Chemokine analogs for the treatment of human diseases

Info

Publication number: 20070066523
Type: Application
Filed: Jul 26, 2006
Publication Date: Mar 22, 2007
Applicant:
Inventors: Ahmed Merzouk (Richmond), Donald Wong (Vancouver), Hassan Salari (Delta)
Application Number: 11/494,232

Abstract

The present invention is concerned with chemokine analogs, including IL-8 analogs, IP-10 analogs, MIP-1α analogs, RANTES analogs, I-309 analogs, MCP-1 analogs, and CCL28 analogs, that are useful for the treatment of a variety of diseases and disorders, and as an adjunct to the treatment of a variety of diseases and disorders. A therapeutically effective amount of the chemokine analog may be administered to a patient in need of such treatment.

Description

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

Not applicable.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

Not applicable.

FIELD OF THE INVENTION

This invention relates to the preparation, design, derivation, and use of peptide agonists and antagonists of chemokines. In one aspect, this invention relates to the preparation, design, derivation, or use of chemokine derivatives, agonists or antagonists of seven human chemokines: IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 (hMEC).

BACKGROUND OF THE INVENTION

Chemokines (chemoattractant cytokines) are a family of homologous serum proteins of between 7 and 16 kDa, which were originally characterized by their ability to induce migration of leukocytes. Most chemokines have four characteristic cysteines (Cys), and depending on the motif displayed by the first two cysteines, they have been classified into CXC or alpha, CC or beta, C or gamma, and CX3C or delta chemokine classes. Two disulfide bonds are formed between the first and third cysteine and between the second and fourth cysteine. In general, it was thought that the disulfide bridges were required, and Clark-Lewis and co-workers reported that, at least for IL-8, the disulfide bridges are critical for chemokine activity (Clark-Lewis et al., J. Biol. Chem. 269:16075-16081, 1994). The only exception to having four cysteines is lymphotactin, which has only two cysteine residues. Thus, lymphotactin manages to retain a functional structure with only one disulfide bond.

In addition, the CXC, or alpha, subfamily has been divided into two groups depending on the presence of the ELR motif (Glu-Leu-Arg) preceding the first cysteine: the ELR-CXC chemokines and the non-ELR-CXC chemokines (see, e.g., Clark-Lewis, supra, and Belperio et al., “CXC Chemokines in Angiogenesis,” J. Leukoc. Biol. 68:1-8, 2000).

ELR-CXC chemokines, such as IL-8, are generally strong neutrophil chemoattractants while non-ELR chemokines, such as IP-10, and SDF-1, predominantly recruit lymphocytes. CC chemokines, such as RANTES, MIP-1-alpha, MCP-1, generally function as chemoattractants for monocytes, basophils, eosinophils, and T-cells but not neutrophils. In general, chemokines are chemotactic agents that recruit leukocytes to the sites of injuries.

Specific Chemokines

IL-8

Interleukin-8 (IL-8 or CXCL8) was first identified in 1987 as a chemokine with the ability to specifically activate neutrophils. Upon exposure to IL-8, neutrophils are activated, and change their shape. Neutrophils are activated by a process that is probably mediated by an increase in intracellular calcium levels. This activation allows neutrophils to migrate across the vascular wall. Secretion of IL-8 can occur from a wide variety of cells, including other leukocytes, fibroblasts, endothelial cells, and epithelial cells in response to ischemia and trauma.

IP-10

Interferon-inducible protein-10 (IP-10 or CXCL10) is induced by interferon-gamma and TNF-alpha, and is produced by keratinocytes, endothelial cells, fibroblasts and monocytes. IP-10 is thought to play a role in recruiting activated T cells to sites of tissue inflammation (Dufour, et al., “IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking,” J Immunol., 168:3195-204, 2002). In addition, IP-10 may play a role in hypersensitivity. It may also play a role in the genesis of inflammatory demyelinating neuropathies (Kieseier, et al., “Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10,” Brain 125:823-34, 2002).

MIP-1α

Macrophage inflammatory protein-1-alpha (MIP-1α, MIP-1-alpha or CCL3) is a factor produced by macrophages in response to their stimulation by bacterial endotoxins. It activates neutrophils, eosinophils, and basophils and appears to play a role in inflammation. Additionally, it is especially potent as a basophil agonist, and appears to act through a rapid rise in intracellular calcium, and causes the release of histamine, sulfido-leukotrienes, and also plays a role in chemotaxis. MIP-1α may also act to inhibit stem cell proliferation.

RANTES

RANTES (Regulated upon Activation, Normal T-cell Expressed, and presumably Secreted or CCL5) is a chemokine that acts on T-cells, eosinophils and basophils and assists in recruiting leukocytes to inflammatory sites. In particular, it increases the adherence of monocytes to endothelial cells, and selectively supports the migration of certain types of leukocytes. In some cases, RANTES has been shown to activate basophils and causes the release of histamines. It may also be involved in the proliferation and activation of certain types of killer cells.

I-309

I-309 refers to the name of a cDNA clone encoding a chemokine (Miller, et al., “A novel polypeptide secreted by activated human T lymphocytes,” J Immunol., 143(9):2907-16, 1989). I-309 is chemotactic for human monocytes, and additionally activates them. However, it appears to have no effect on neutrophils.

MCP-1

Monocyte chemoattractant (or chemotactic) protein-1 (monocyte chemotactic protein-1, MCP-1 or CCL2) is another CCL chemokine. It is expressed by monocytes, endothelial cells, smooth muscle cells, and certain types of epithelial cells in culture. The expression of MCP1 is induced in human peripheral blood mononuclear leukocytes by phytohemagglutinin (PHA), lipopolysaccharide, and IL1. MCP-1 functions as a chemoattractant for monocytes but not neutrophils. There have been reports that two point mutations are sufficient for MCP-1 to become chemotactic for neutrophils. MCP-1 activates monocytes and macrophages in vivo, as well as basophils. Additionally, it can induce the proliferation and activation of certain types of killer cells.

CCL28

CCL28 (hMEC) is a recently described CC chemokine which may play a particularly important role in homeostasis or inflammatory responses in the gastrointestinal system (Wang et al., J. Biol. Chem. 275:22313-23, 2000).

SDF-1

Stromal cell-derived factor-1 (SDF-1 or CXCL12) is a CXC chemokine that demonstrates in vitro activity with respect to lymphocytes and monocytes but not neutrophils. It is a highly potent in vivo chemoattractant for mononuclear cells. SDF-1 has been shown to induce intracellular actin polymerization in lymphocytes, and to induce a transient elevation of cytoplasmic calcium in some cells.

Chemokine Receptors

The receptors for chemokines are G-protein coupled seven-transmembrane receptors. Based on the chemokine class they bind, the receptors have been named CXCR1, CXCR2, CXCR3, CXCR4, and CXCR5 (all of which bind CXC chemokines); CCR1 through CCR9 (all of which bind CC chemokines); XCR1 (which binds the C chemokine, Lptn); and CX3CR1 (which binds the CX3C chemokine, fractalkine or neurotactin (See Table 1)).

The chemokines and their receptors have received increasing attention in the last few years. In addition to their role in HIV pathogenesis, it is now clear that chemokines participate in many pathological conditions such as inflammation and diseases or conditions associated with autoinimune responses. They also play a very important role in normal homeostasis, including lymphoid development and migration, and the growth of bone. As a result of their role in various physiological processes and pathological conditions and diseases, chemokines have important potential therapeutic applications.

TABLE 1 Chemokine receptors Human chemokine ligands CXCR1 IL-8, GCP-2 CXCR2 IL-8, GCP-2, Gro α, Gro β, Gro γ, ENA-78, PBP CXCR3 MIG, IP-10, I-TAC CXCR4 SDF-1/PBSF CCR1 MIP-1 α, MIP-1 β, RANTES, HCC-1, 2, 3, and 4 CCR2 MCP-1, MCP-2, MCP-3, MCP-4 CCR3 Eotaxin-1 eotaxin-2, MCP-3 CCR4 TARC, MDC, MIP-1 α, RANTES CCR5 MIP-1 α, MIP-1 β, RANTES CCR6 MIP-3 α/LARC CCR7 MIP-3 β/ELC, 6Ckine/LC CCR8 I-309 CCR9 TECK CCR10 CCL27, CCL28(hMEC)

SUMMARY OF THE INVENTION

This invention relates in one aspect to the design, preparation, derivation, and use of peptide agonists and antagonists of chemokines referred to herein as chemokine analogs. In preferred embodiments, this invention relates to the design, preparation, derivation, or use of peptide agonists or antagonists of a chemokine selected from the group consisting of IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 (hMEC). In other preferred embodiments, the invention relates to the design, preparation, derivation, or use of chemokine analogs derived from one or more of the seven chemokines: IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28. Particularly preferred embodiments are set forth infra in the Detailed Description of the Invention, Examples and Claims.

Another aspect of the invention is directed towards a method for treating disease, disorder or abnormal condition comprising administering to a patient in need of such treatment a therapeutically effective amount of a chemokine analog having a structure selected from the group consisting of sequence al (SEQ ID NO:9) to sequence a 154 (SEQ ID NO:162), inclusive; sequence b1 (SEQ ID NO:163) to sequence b575 (SEQ ID NO:728), inclusive; sequence c1 (SEQ ID NO:729) to sequence c160 (SEQ ID NO:881), inclusive; sequence d1 (SEQ ID NO:882) to sequence d90 (SEQ ID NO:971), inclusive; sequence e1 (SEQ ID NO:972) to sequence e382 (SEQ ID NO:1350), inclusive; sequence g2 (SEQ ID NO:1351) to sequence g97 (SEQ ID NO:1446), inclusive; and sequence h1 (SEQ ID NO:1447) to sequence h184 (SEQ ID NO:1631), inclusive, in a pharmaceutically acceptable carrier.

In preferred embodiments, said disease, disorder or abnormal condition is selected from the group consisting of autoimmune diseases, acute chronic inflammation, cancer, cardiovascular disease, infectious disease, and inflammatory disorders including rheumatoid arthritis, chronic inflammatory bowel disease, chronic inflammatory pelvic disease, multiple sclerosis, asthma, osteoarthritis, atherosclerosis, psoriasis, rhinitis, autoimmunity, and organ transplant rejection. In other preferred embodiments, the administration of the compound of the invention serves to increase the hemocrit, assist in mobilizing and recovering stem cells, stimulate the production of blood cells, assist in vaccine production, or assist in gene therapy.

A further aspect of this invention relates to therapeutic uses of chemokine analogs to cure, to manage, or to prevent a disease or disorder selected from the group consisting of autoimmune diseases, acute chronic inflammation, cancer, cardiovascular disease, infectious disease, and inflammatory disorders including rheumatoid arthritis, chronic inflammatory bowel disease, chronic inflammatory pelvic disease, multiple sclerosis, asthma, osteoarthritis, atherosclerosis, psoriasis, rhinitis, autoimmunity, and organ transplant rejection. A further aspect of this invention relates to therapeutic uses of chemokine analogs to increase the hemocrit, assist in mobilizing and recovering stem cells, stimulate the production of blood cells, or assist in vaccine production.

Another aspect of the invention is directed towards providing pharmaceutical compositions of chemokine analogs in order to treat a mammal by enhancing or inhibiting the action of a chemokine on its receptor. An additional aspect of the invention relates to the use of pharmaceutical compositions of analogs of human IL-8, EP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28 to treat a human by enhancing or inhibiting the action of IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28 on its respective receptor.

A still further aspect of the invention is a method for modulating the activity of a chemokine receptor by contacting this chemokine receptor with a compound comprising a structure selected from the group consisting sequence a1 (SEQ ID NO:9) to sequence a154 (SEQ ID NO:162), inclusive; sequence b1 (SEQ ID NO:163) to sequence b575 (SEQ ID NO:728), inclusive; sequence c1 (SEQ ID NO:729) to sequence c160 (SEQ ID NO:881), inclusive; sequence d1 (SEQ ID NO:882) to sequence d90 (SEQ ID NO:971), inclusive; sequence e1 (SEQ ID NO:972) to sequence e382 (SEQ ID NO:1350), inclusive; sequence g2 (SEQ ID NO:1351) to sequence g97 (SEQ ID NO:1446), inclusive; and sequence h1 (SEQ ID NO:1447) to sequence h184 (SEQ ID NO:1631), inclusive.

Another aspect of the invention consists of using the chemokine analogs of the invention to treat a patient so as to (a) mobilize intracellular calcium in the patient, (b) mobilize leukocytes or more specifically, neutrophils, or (c) decrease the toxic effects of a cytotoxic agent on white blood cells, leukocytes and/or hematopoietic cells.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a concentration-dependent inhibition of ¹²⁵I-IL-8 binding to CXCR1 and CXCR2 by IL-8, indicating the affinity of IL-8 for the CXCR1 and CXCR2 receptors. FIG. 1 also shows the binding of the IL-8 peptide analogs (competing ligands described in Example 1) to CXCR1 and/or CXCR2 receptors on THP-1 cells, a human monocytoid cell line. THP-1 cells were preincubated with IL-8 or IL-8 analog for 30 min, then were assessed for ¹²⁵I-IL-8 binding following 2 hr of incubation with ¹²⁵I-IL-8. 10 nM of ¹²⁵I-IL-8 was added in the presence of IL-8 or the indicated analogs at the concentrations illustrated. The results are expressed as percentages of the maximal specific binding that was determined without competing ligand.

FIG. 2 shows the induction of [Ca²⁺]_imobilization by I-309 and I-309 analogs. Fluo-4,AM loaded human peripheral blood mononuclear cells (5×10⁶/ml) were stimulated with I-309, Compounds 4, 5, 6, and 7 at the concentrations indicated. The values represent the mean+/−one S.D.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to the design, preparation, derivation, and use of chemokine analogs. In one aspect, this invention is directed to the synthesis or use of chemokine analogs which bind to receptors for any of seven human chemokines: IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 (hMEC). In another aspect, the invention is directed to the synthesis, design, derivation, or use of chemokine analogs or derivatives of one or more of the seven human chemokines: IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 (hMEC). In a further aspect, the invention is directed to the synthesis, design, derivation, or use of agonist or antagonist analogs of one or more of the following seven human chemokines: IL-8, EP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28, and derivatives thereof. The invention is not limited in its application to the details of structures and the arrangements of components set forth in the following description or illustrated in the drawings and the figures. Further, it should be understood that in any claimed list or claimed Markush group, those schooled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the list or Markush group. Additionally, any individual member of the claimed list or the claimed Markush group can be removed from the list or Markush group without affecting the patentability of the remaining members.

The sequences of the seven aforementioned human chemokines are shown below. First are two CXC chemokines: IL-8, and IP-10; second are five CC chemokines: MIP-1α, MCP-1, RANTES, I-309, and CCL28.

IL-B: Ala-Val-Ile-Pro-Arg-Ser-Ala- (SEQ ID NO:1) Lys-Glu-Leu-Arg-Cys-Gln-Cys- Ile-Lys-Thr-Tyr-Ser-Lys-Pro- Phe-His-Pro-Lys-Phe-Ile-Lys- Glu-Leu-Arg-Val-Ile-Glu-Ser- Gly-Pro-His-Cys-Ala-Asn-Thr- Glu-Ile-Ile-Val-Lys-Leu-Ser- Asp-Gly-Arg-Glu-Leu-Cys-Leu- Asp-Pro-Lys-Glu-Asn-Trp-Val- Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn-Ser IP-10: Val-Pro-Leu-Ser-Arg-Thr-Val- (SEQ ID NO:2) Arg-Cys-Thr-Cys-Ile-Ser-Ile- Ser-Asn-Gln-Pro-Val-Asn-Pro- Pro-Arg-Ser-Leu-Glu-Lys-Leu- Glu-Ile-Ile-Pro-Ala-Ser-Gln- Phe-Cys-Pro-Arg-Val-Glu-Ile- Ile-Ala-Thr-Met-Lys-Lys-Lys- Gly-Glu-Lys-Arg-Cys-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser- Pro MIP-1α Ser-Leu-Ala-Ala-Asp-Thr-Pro- (SEQ ID NO:3) Thr-Ala-Cys-Cys-Phe-Ser-Tyr- Thr-Ser-Arg-Gln-Ile-Pro-Gln- Asn-Phe-Ile-Ala-Asp-Tyr-Phe- Glu-Thr-Ser-Ser-Gln-Cys-Ser- Lys-Pro-Gly-Val-Ile-Phe-Leu- Thr-Lys-Arg-Ser-Arg-Gln-Val- Cys-Ala-Asp-Pro-Ser-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Ser- Asp-Leu-Glu-Leu-Ser-Ala RANTES: Ser-Pro-Tyr-Ser-Ser-Asp-Thr- (SEQ ID NO:4) Thr-Pro-Cys-Cys-Phe-Ala-Tyr- Ile-Ala-Arg-Pro-Leu-Pro-Arg- Ala-His-Ile-Lys-Glu-Tyr-Phe- Tyr-Thr-Ser-Gly-Lys-Cys-Ser- Asn-Pro-Ala-Val-Val-Phe-Val- Thr-Arg-Lys-Asn-Arg-Gln-Val- Cys-Ala-Asn-Pro-Glu-Lys-Lys- Trp-Val-Arg-Glu-Tyr-Ile-Asn- Ser-Leu-Glu-Met-Ser I-309: Lys-Ser-Met-Gln-Val-Pro-Phe- (SEQ ID NO:5) Ser-Arg-Cys-Cys-Phe-Ser-Phe- Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg- Asn-Thr-Ser-Ser-Ile-Cys-Ser- Asn-Glu-Gly-Leu-Ile-Phe-Lys- Leu-Lys-Arg-Gly-Lys-Glu-Ala- Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys- Met-Leu-Arg-His-Cys-Pro-Ser- Lys-Arg-Lys MCP-1: Gln-Pro-Asp-Ala-Ile-Asn-Ala- (SEQ ID NO:7) Pro-Val-Thr-Cys-Cys-Tyr-Asn- Phe-Thr-Asn-Arg-Lys-Ile-Ser- Val-Gln-Arg-Leu-Ala-Ser-Tyr- Arg-Arg-Ile-Thr-Ser-Ser-Lys- Cys-Pro-Lys-Glu-Ala-Val-Ile- Phe-Lys-Thr-Ile-Val-Ala-Lys- Glu-Ile-Cys-Ala-Asp-Pro-Lys- Gln-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln- Thr-Gln-Thr-Pro-Lys-Thr CCL28: Ile-Leu-Pro-Ile-Ala-Ser-Ser- (SEQ ID NO:8) Cys-Cys-Thr-Glu-Val-Ser-His- His-Ile-Ser-Arg-Arg-Leu-Leu- Glu-Arg-Val-Asn-Met-Cys-Arg- Ile-Gln-Arg-Ala-Asp-Gly-Asp- Cys-Asp-Leu-Ala-Ala-Val-Ile- Leu-His-Val-Lys-Arg-Arg-Arg- Ile-Cys-Val-Ser-Pro-His-Asn- His-Thr-Val-Lys-Gln-Trp-Met- Lys-Val-Gln-Ala-Ala-Lys-Lys- Asn-Gly-Lys-Gly-Asn-Val-Cys- His-Arg-Lys-Lys-His-His-Gly- Lys-Arg-Asn-Ser-Asn-Arg-Ala- His-Gln-Gly-Lys-His-Glu-Thr- Tyr-Gly-His-Lys-Thr-Pro-Tyr

The N-terminal region of chemokines is involved in the binding and activating site of its receptor, as well as is the carboxy terminal region. The beta sheet structure that connects the two termini appears to play a role in the stabilization of the CXCR and assuring that the termini are in the proper conformation.

Examples of these analogs are compounds containing structures corresponding to various regions or portions of the chemokines. In preferred embodiments, the chemokine analog comprises an N-terminal region and a C-terminal region joined together by means of a linker. In other preferred embodiments, the amino-acid residues of the chemokine or chemokine analog are cyclized, e.g., by etherification of lysine and serine residues or by other means described infra or known in the art. In still other preferred embodiments, the chemokine analog comprises a sequence derived from the wild-type chemokine sequence but with one or more of the cysteines replaced with another amino acid including natural and non-natural amino acids). Other preferred embodiments include chemokine analogs comprising an N-terminal region, an internal region containing up to three anti-parallel β-sheets, a C-terminal region containing an α-helical structure, a combination of the N- and C-terminal regions linked together directly, a combination of a N-terminal and internal region, or a combination of an internal and C-terminal region, or finally a combination of N-terminal, internal and C-terminal regions. The regions selected from the N-terminal, internal and C-terminal regions may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20, 25, 30, 35, 40, 41, or 45 amino acids in length.

Examples of such analogs also include a cross combination of one chemokine region to a different region from a different chemokine in the same or different family. These examples include, but are not limited to, regions of two CXC chemokines: IL-8, IP-10, and five CC chemokines: MIP-1α, MCP-1, RANTES, I-309, and CCL28.

Chemokine analogs of the invention are useful for treating or preventing inflammatory conditions, autoimmune disorders, cancer, graft rejection, bacterial infection, viral infection, vascular conditions (for example, atherosclerosis, restenosis, systemic lupus erythematosis, and ischemia-reperfusion), sepsis, tumorigenesis, and angiogenesis; stem cell mobilization as well as vaccine production and blood cell recovery following chemotherapy. Inflammatory conditions contemplated by the present invention include both acute and chronic inflammatory diseases. Chemokine analogs of the inventions may also prove useful in conducting gene therapy; one manner they may assist in the methods of gene therapy is through an arrest of the cell cycle.

Examples of uses of the chemokine analogs in some aspects of the invention include, but are not limited to, treatment or management of arthritis, asthma, colitis/illeitis, psoriasis, atherosclerosis and the like. Examples of uses of the chemokine analogs in some aspects of the invention to treat or manage autoimmune conditions include, but are not limited to, rheumatoid arthritis, multiple sclerosis and other autoimmunological diseases. Examples of uses of the chemokine analogs in some aspects of the invention to treat or manage cancer include, but are not limited to, treatment or management of human malignancy/cancer cell metastasis and relapses. Examples of uses of the chemokine analogs in some aspects of the invention to assist in blood cell recovery include, but are not limited to, blood cell elevation after chemotherapy/radiotherapy and stem cell mobilization for transplantations. Examples of uses of the chemokine analogs in some aspects of the invention for vaccine production include, but are not limited to, enhancement in humoral antibody production, increases in antigen presenting T-cells, increases in dendritic cells and immunological features known as vaccine induction. Chemokines may also play a role in osteoporosis and thus osteoporosis may be treated by chemokine analogs of the invention. Chemokine analogs of the invention may also prove useful in treating genetic disease through gene therapy.

As defined by the present invention a chemokine analog acts as an agonist or an antagonist to a native chemokine. The agonistic activity of the chemokine analogs of the present invention includes mimicking of biological activity induced by corresponding native chemokines. The antagonistic activity of the chemokine analogs of the present invention includes inhibition of biological activity induced by native chemokines. The instant invention also encompasses a chemokine analog that acts as an agonist or an antagonist to a different native chemokine.

Peptides

In this application, the products of the present invention are referred to by various terms, including “analogs” of the present invention, “chemokine mimetics,” “chemokine analogs,” and “chemokine derivatives.” These terms are used interchangeably and denote equivalent compounds. The term “polypeptides of the present invention,” may also be used herein to refer to chemokine analogs. Chemokine analogs of the present invention comprise a structure which comprises a sequence selected from the group set forth as SEQ ID NO:9 through SEQ ID NO:1631, and thus may comprise additional elements such as R-group substituents and a linker selected from the possibilities set forth in the instant invention.

As defined by the present invention, biological activity refers to the biological activity of the native chemokines, as defined and measured by the scientific reports known to those of skill in the art, and exemplified in the following review articles (Bruce, L. et al., “Radiolabeled Chemokine binding assays,” Methods in Molecular Biology (2000) vol. 138, pp129-134, Raphaele, B. et al. “Calcium Mobilization,” Methods in Molecular Biology (2000) vol. 138, pp143-148, Paul D. Ponath et aL, “Transwell Chemotaxis,” Methods in Molecular Biology (2000) vol. 138, pp113-120 Humana Press. Totowa, N.J.). Aspects of biological activity include, but are not limited to, receptor binding, chemotaxis, calcium mobilization, along with other activities recognized by those of skill in the art.

The amino acids are identified in the present application by the conventional one-letter and three-letter abbreviations as indicated below, and are preceded by “L-” to indicate their L-form and by “D-” to refer to their D form. These abbreviations are generally accepted in the peptide art as recommended by the IUPAC-IUB commission in biochemical nomenclature:

Alanine A Ala Leucine L Leu Arginine R Arg Lysine K Lys Asparagine N Asn Methionine M Met Aspartic acid D Asp Phenylalanine F Phe Cysteine C Cys Proline P Pro Glutamic acid E Glu Serine S Ser Glutamine Q Gln Threonine T Thr Glycine G Gly Tryptophan W Trp Histidine H His Tyrosine Y Tyr Isoleucine I Ile Valine V Val Ornithine O Orn

All of the peptide sequences set out herein are written according to the generally accepted convention whereby the N-terminal amino acid is on the left and the C-terminal amino acid is on the right.

Chemokine mimetics of the invention may include chemokine derivatives or chemokine analogs and their derivatives, such as C-terminal hydroxymethyl derivatives, O-modified derivatives (e.g., C-terminal hydroxymethyl benzyl ether), N-terminally modified derivatives including substituted amides such as alkylamides and hydrazides and compounds in which a C-terminal phenylalanine residue is replaced with a phenethylamide analogue (e.g., Ser-Ile-phenethylamide as an analog of the tripeptide Ser-Ile-Phe), glycosylated chemokine derivatives, polyethylene glycol modified derivatives, or biotinylated derivatives. Chemokine analogs of the invention include pharmaceutically acceptable salts of the chemokine analogs.

Modifying Groups

In one aspect of the invention, the chemokine analogs of the invention, (such as peptides derived from IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28) may be coupled directly or indirectly to at least one modifying group. In some aspects of the invention, the term “modifying group” is intended to include structures that are directly attached to the peptidic structure (e.g., by covalent bonding or covalent coupling), as well as those that are indirectly attached to the peptidic structure (e.g., by a stable non-covalent bond association or by covalent coupling through a linker to additional amino acid residues). In other aspects of the invention the term “modifying group” may also refer to mimetics, analogues or derivatives thereof, which may flank the IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28 core peptidic structure. For example, the modifying group can be coupled to the amino-terminus or carboxy-terminus of an IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28 peptidic structure, or to a peptidic or peptidomimetic region flanking the core structure. Alternatively, the modifying group can be coupled to a side chain of at least one amino acid residue of an IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28 peptidic structure, or to a peptidic or peptido-mimetic region flanking the core domain (e.g., through the epsilon amino group of a lysyl residue(s); through the carboxyl group of an aspartic acid residue(s) or a glutamic acid residue(s); through a hydroxy group of a tyrosyl residue(s), a serine residue(s) or a threonine residue(s); or any other suitable reactive group on an amino acid side chain). In other aspects, modifying groups covalently coupled to the peptidic structure can be attached by means and using methods well known in the art for linking chemical structures, including, for example, amide, alkylamino, sulfide, carbamate or urea bonds.

In some embodiments, the modifying group may comprise a cyclic, heterocyclic or polycyclic group. The term “cyclic group,” as used herein, includes cyclic saturated or unsaturated (i.e., aromatic) group having from 3 to 10; from 4 to 8; or 5, 6, or 7 carbon atoms. Exemplary non-aromatic cyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cyclooctyl. The term “heterocyclic group” includes optionally substituted, saturated or unsaturated, three- to eight-membered cyclic structures in which one or more skeletal atoms is oxygen, nitrogen, sulfur, or combinations thereof. Cyclic groups may be unsubstituted or substituted at one or more ring positions. A cyclic group may for example be substituted with halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls, arylalkyls, heterocycles, hydroxyls, aminos, nitros, thiols amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates, selenoethers, ketones, aldehydes, esters, —CF₃, —CN. The cyclic group may also be linked to a substituent, such as halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls, arylalkyls, heterocycles, hydroxyls, aminos, nitros, thiols amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates, selenoethers, ketones, aldehydes, esters, —CF₃, or —CN, by means of a saturated or unsaturated chain of 1, 2, 3, 4, 5, 6, 7, 8, or more carbon atoms; additionally one or more of the carbon atoms may be replaced with an oxygen, nitrogen, or sulfur atom. Other means of linking these groups are also possible.

In one embodiment of the invention, chemokines and chemokine analogs are designed by replacing all or part of the beta-sheet domain with a linker. In a different embodiment, all or a portion of the amino-terminal domain aid all or a portion of the carboxy-terminal domain of a chemokine or chemokine analog are connected with a linker. In another embodiment, the chemokines and chemokine analogs are designed so that there are cyclized by covalent modification between residues of the peptide. In still other embodiments, the cysteines of the chemokines are replaced by other amino acids. In further embodiments, chemokines and chemokine analogs are modified by attaching modifying groups to the amino terminus.

Definitions

The term “heterocyclic group” includes cyclic saturated, unsaturated and aromatic groups having from 3 to 10; from 4 to 8; or 5, 6, or 7 carbon atoms, wherein the ring structure includes about one or more heteroatoms. Heterocyclic groups include pyrrolidine, oxolane, thiolane, imidazole, oxazole, piperidine, piperazine, morpholine. The heterocyclic ring may be substituted at one or more positions with such substituents as, for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls, arylalkyls, other heterocycles, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, —CF₃, —CN. Heterocycles may also be bridged or fused to other cyclic groups as described below. A linker may also link the heterocyclic group to such substituents as, for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, aryls, arylalkyls, heterocycles, hydroxyls, aminos, nitros, thiols amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates, selenoethers, ketones, aldehydes, esters, —CF₃, —CN.

The term “polycyclic group” as used herein is intended to refer to two or more saturated, unsaturated or aromatic cyclic rings in which two or more carbons are common to two adjoining rings, so that the rings are “fused rings.” Rings that are joined through non-adjacent atoms are termed “bridged” rings. Each of the rings of the polycyclic group may be substituted with such substituents as described above, as for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, —CF₃, or —CN.

The term “alkyl” refers to a saturated aliphatic groups, including straight chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. In some embodiments, a straight chain or branched chain alkyl has 20 or fewer carbon atoms in its backbone (C₁-C₂₀for straight chain, C₃-C₂₀for branched chain), or 10 or fewer carbon atoms. In some embodiments, cycloalkyls may have from 4-10 carbon atoms in their ring structure, such as rings made from 5, 6 or 7. Unless the number of carbons is otherwise specified, “lower alkyl” as used herein means an alkyl group, as defined above, having from one to ten carbon atoms in its backbone structure. Likewise, “lower alkenyl” and “lower alkynyl” have chain lengths of ten or less carbons.

The term “alkyl” (or “lower alkyl”) as used throughout the specification and claims is intended to include both “unsubstituted alkyls” and “substituted alkyls,” the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, halogen, hydroxyl, carbonyl (such as carboxyl, ketones (including alkylcarbonyl and arylcarbonyl groups)), and esters (including alkyloxycarbonyl and aryloxycarbonyl groups), thiocarbonyl, acyloxy, alkoxyl, phosphoryl, phosphonate, phosphinate, amino, acylamino, amido, amidine, imino, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. The moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. For instance, the substituents of a substituted alkyl may include substituted and unsubstituted forms of aminos, azidos, iminos, amidos, phosphoryls (including phosphonates and phosphinates), sulfonyls (including sulfates, sulfonamidos, sulfamoyls and sulfonates), or silyl groups, as well as ethers, alkylthios, carbonyls (including ketones, aldehydes, carboxylates, and esters), —CF₃, —CN and the like. Exemplary substituted alkyls are described below. Cycloalkyls can be further substituted with alkyls, alkenyls, alkoxys, alkylthios, aminoalkyls, carbonyl-substituted alkyls, —CF3, —CN, and the like.

The terms “alkenyl” and “alkynyl” refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.

The term “aralkyl,” as used herein, refers to an alkyl or alkylenyl group substituted with at least one aryl group. Exemplary aralkyls include benzyl (i.e., phenylmethyl), 2-naphthylethyl, 2-(2-pyridyl)propyl, 5-dibenzosuberyl, and the like.

The term “alkylcarbonyl,” as used herein, refers to —C(O)-alkyl. Similarly, the term “arylcarbonyl” refers to —C(O)-aryl. The term “alkyloxycarbonyl,” as used herein, refers to the group —C(O)—O-alkyl, and the term “aryloxycarbonyl” refers to —C(O)—O-aryl. The term “acyloxy” refers to —O—C(O)—R₇, in which R₇is alkyl, alkenyl, alkynyl, aryl, aralkyl or heterocyclyl.

The term “amino,” as used herein, refers to —N(R_α)(R_β), in which R_α and R_β are each independently hydrogen, alkyl, alkyenyl, alkynyl, aralkyl, aryl, or in which R_α and R_β together with the nitrogen atom to which they are attached form a ring having 4-8 atoms. Thus, the term “amino,” as used herein, includes unsubstituted, monosubstituted (e.g., monoalkylamino or monoarylamino), and disubstituted (e.g., dialkylamino or alkylarylamino) amino groups. The term “amido” refers to —C(O)—N(R_α)(R_β), in which R_α and R_β are as defined above. The term “acylamino” refers to —N(R′_α)C(O)—R₇, in which R₇is as defined above and R_α is alkyl.

As used herein, the term “nitro” means —NO₂; the term “halogen” designates —F, —Cl, —Br or —I; the term “sulfhydryl” means —SH; and the term “hydroxyl” means —OH.

The term “aryl” as used herein includes 5-, 6- and 7-membered aromatic groups that may include from zero to four heteroatoms in the ring, for example, phenyl, pyrrolyl, furyl, thiophenyl, imidazolyl, oxazole, thiazolyl, triazolyl, pyrazolyl, pyridyl, pyrazinyl, pyridazinyl and pyrimidinyl, and the like. Those aryl groups having heteroatoms in the ring structure may also be referred to as “aryl heterocycles” or “heteroaromatics.” The aromatic ring can be substituted at one or more ring positions with such substituents as described above, as for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, —CF₃, —CN, or the like. Aryl groups can also be part of a polycyclic group. For example, aryl groups include fused aromatic moieties such as naphthyl, anthracenyl, quinolyl, indolyl, and the like.

Modifying groups may also include groups comprising biochemical labels or structures, such as biotin, fluorescent-label-containing groups, light scattering or plasmon resonant particle, a diethylene-triaminepentaacetyl group, a (O)-menthoxyacetyl group, a N-acetylneuraminyl group, a cholyl structure or an iminobiotinyl group. A chemokine analog or chemokine mimetic compound may be modified at its carboxy terminus with a cholyl group according to methods known in the art. Cholyl derivatives and analogs may also be used as modifying groups. For example, a preferred cholyl derivative is Aic (3-(O-aminoethyl-iso)-cholyl), which has a free amino group that can be used to further modify the chemokine mimetic compound. A modifying group may be a “biotinyl structure,” which includes biotinyl groups and analogues and derivatives thereof (such as a 2-iminobiotinyl group). In another embodiment, the modifying group may comprise a fluorescent-label group, e.g., a fluorescein-containing group, such as a group derived from reacting an IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 derived peptidic structure with 5-(and 6-)-carboxyfluorescein, succinimidyl ester or fluorescein isothiocyanate. The chemokine analogs may also be modified by attaching other fluorescent labels including rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin and energy transfer fluorescent dyes or fluorescent ion-indicators. In various other embodiments, the modifying group(s) may comprise an N-acetylneurarninyl group, a trans4-cotininecarboxyl group, a 2-imino-1-imidazolidineacetyl group, an (S)-(−)-indoline-2-carboxyl group, a (−)-menthoxyacetyl group, a 2-norbornaneacetyl group, a γ-oxo-5-acenaphthenebutyryl, a (−)-2-oxo-4-thiazolidinecarboxyl group, a tetrahydro-3-furoyl group, a 2-iminobiotinyl group, a diethylenetriaminepentaacetyl group, a 4-morpholinecarbonyl group, a 2-thiopheneacetyl group or a 2-thiophenesulfonyl group. In other embodiments, light scattering groups, magnetic groups, nanogold, other proteins, a solid matrix, radiolabels, or carbohydrates may be attached.

In still other aspects, the modifying group. may be an oligomer, for example, polyethylene glycol, an oligonucleotide, a polypeptide (which may or may not be derived from a chemokine) or one moiety of a binding pair.

Functional Enhancement

A chemokine analog compound of the invention may be further modified to alter the specific properties of the compound while retaining the desired functionality of the compound. For example, in one embodiment, the compound may be modified to alter a pharmacokinetic property of the compound, such as in vivo stability, solubility, bioavailability or half-life. The compound may be modified to label the compound with a detectable substance. The compound may be modified to couple the compound to an additional therapeutic moiety. To further chemically modify the compound, such as to alter its pharmacokinetic properties, reactive groups can be derivatized. For example, when the modifying group is attached to the amino-terminal end of the IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 core domain, the carboxy-terminal end of the compound may be further modified. Potential C-terminal modifications include those that reduce the ability of the compound to act as a substrate for carboxypeptidases. Examples of C-terminal modifiers include an amide group, an ethylamide group and various non-natural amino acids, such as D-amino acids, β-alanine, C-terminal decarboxylation, and a C-terminal alcohol. Alternatively, when the modifying group is attached to the carboxy-terminal end of the aggregation core domain, the amino-terminal end of the compound may be further modified, for example, to reduce the ability of the compound to act as a substrate for aminopeptidases.

Chemokines and chemokine analogs of the invention may be modified by the addition of polyethylene glycol (PEG). PEG modification may lead to improved circulation time, improved solubility, improved resistance to proteolysis, reduced antigenicity and immunogenicity, improved bioavailability, reduced toxicity, improved stability, and easier formulation (For a review see, Francis et al., International Journal of Hematology 68:1-18, 1998). PEGylation may also result in a substantial reduction in bioactivity.

The chemokine analogs of the invention may also be coupled to a radioisotope such as yttrium-90 or iodine-131 for therapeutic purposes (see, e.g., DeNardo et al., “Choosing an optimal radioinmmunotherapy dose for clinical response,” Cancer 94(4 Suppl):1275-86, 2002; Kaltsas et al., “The value of radiolabelled MIBG and octreotide in the diagnosis and management of neuroendocrine tumours,” Ann Oncol 12 Suppl 2:S47-50, 2001).

Detection Enhancement

A chemokine mimetic compound can be further modified to label the compound by reacting the compound with a detectable substance. In some aspects of the invention, suitable detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, light scattering or ptasmon resonant materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase. Examples of suitable prosthetic groups which are members of a binding pair and are capable of forming complexes include streptavidin/biotin, avidinibiotin and an antigen/antibody complex (e.g., rabbit IgG and anti-rabbit IgG). Examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin and energy transfer fluorescent dyes. An example of a luminescent material includes luminol. Examples of light scattering or plasmon resonant materials include gold or silver particles and quantum dots. Examples of suitable radioactive material include ¹⁴C, ¹²³I, ₁₂₄I, ₁₂₅I, ₁₃₁I, Tc99m, ₃₅S or ³H. A chemokine mimetic compound may be radioactively labeled with ¹⁴C, either by incorporation of ¹⁴C into the modifying group or one or more amino acid structures in the chemokine mimetic compound. Labeled chemokine mimetic compounds may be used to assess the in vivo phannacokinetics of the compounds, as well as to detect disease progression or propensity of a subject to develop a disease, for example for diagnostic purposes. Tissue distribution chemokine receptors can be detected using a labeled chemokine mimetic compound either in vivo or in an in vitro sample derived from a subject. For use as an in vivo diagnostic agent, a chemokine mimetic compound of the invention may be labeled with radioactive technetium or iodine. A modifying group can be chosen that provides a site at which a chelation group for the label can be introduced, such as the Aic derivative of cholic acid, which has a free amino group. For example, a tyrosine residue within the IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 sequence may be substituted with radioactive iodotyrosyl. Any of the various isotopes of radioactive iodine may be incorporated to create a diagnostic or therapeutic agent. ¹²³I (half-life=13.2 hours) may be used for whole body scintigraphy, ¹²⁴I (half life=4 days) may be used for positron emission tomography (PET), ¹²⁵I (half life=60 days) may be used for metabolic turnover studies and ¹³¹I (half life=8 days) may be used for whole body counting and delayed low resolution imaging studies.

Prodrug

In an alternative chemical modification, a chemokine analog compound of the invention may be prepared in a “prodrug” form, wherein the compound itself does not act as a chemokine analog agonist, but rather is capable of being transformed, upon metabolism in vivo, into a chemokine analog agonist or antagonist compound as defined herein. For example, in this type of compound, the modifying group can be present in a prodrug form that is capable of being converted upon metabolism into the form of an active chemokine analog agonist. Such a prodrug form of a modifying group is referred to herein as a “secondary modifying group.” A variety of strategies are known in the art for preparing peptide prodrugs that limit metabolism in order to optimize delivery of the active form of the peptide-based drug.

Synthesis

Chemokine analog compounds of the invention may be prepared by standard techniques known in the art. A peptide or polypeptide component of a chemokine analog may comprise, at least in part, a peptide synthesized using standard techniques (such as those described by Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., and Baggiolini, M., (1994) J. Biol. Chem., 269, 16075-16081). Automated peptide synthesizers are commercially available (e.g., Advanced ChemTech Model 396; Milligen/Biosearch 9600, Appliedbiosystems/Pioneer). Peptides and polypeptides may be assayed for chemokine receptor agonist or antagonist activity in accordance with standard methods. Peptides and polypeptides may be purified by HPLC and analyzed by mass spectrometry. Peptides and polypeptides may be dimerized. In one embodiment, peptides and polypeptides are dimerized via a disulfide bridge formed by gentle oxidation of the cysteines using 10% DMSO in water. Following HPLC purification, dimer formation may be verified, by mass spectrometry. One or more modifying groups may be attached to a MCP-1, RANTES, IL-8, IP-10, MIP-1α, I-309, or CCL28-derived peptidic component by standard methods, for example, using methods for reaction through an amino group (e.g., the alpha-amino group at the amino-terminus of a peptide), a carboxyl group (e.g., at the carboxy terminus of a peptide), a hydroxyl group (e.g., on a tyrosine, serine or threonine residue) or other suitable reactive group on an amino acid side chain.

In alternative embodiments, analogs derived from the C-terminal and N-terminal joined by a linker could be cyclized in their C-terminal moiety using side-chain to side-chain; side-chain to scaffold or, scaffold to scaffold cyclization. In some embodiments, lactamization, etherification, or RCM (Ring Closing Methatesis) are used to carry out this reaction.

For instance, chemokine analogs may be cyclized using a lactam formation procedure by joining the γ-carboxy side chain or the α-carboxy moiety of glutamate (Glu) residue to the ε-amino side chain of lysine (Lys) residue, as indicated in the following sequences by underlining of linked residues. Lactams may for example be formed between glutamic acid and lysine (Lys) in the C-terminal portion of the polypeptide (which does not correspond necessarily with the numbering of that residue in the native sequence). In further alternatives, a lysine (Lys) may be substituted by ornithine (Orn) or any other (Lor D) natural or (L or D) non-natural amino acid having an amino group on its side chain. Similarly, glutamate (Glu) may for example be substituted with aspartate (Asp), denoted by nomenclature such as (Glu->Asp) indicating a substitution in a given position in the peptide wherein aspartate replaces glutamate.

The chemokine analogs of the invention include chemokine polypeptide sequences wherein one or more of the amino acids have been replaced by a conservative amino acid substitution. The term “conservative amino acid substitution” refers to a polypeptide chain in which one of the amino acid residues is replaced with an amino acid residue having a side chain with similar properties. Families of amino acid residues having side chains with similar properties are well known in the art. These families include amino acids with acidic side chains (e.g., aspartic acid, glutamic acid), basic side chains (e.g., lysine, arginine, histidine), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, an amino acid residue in a chemokine is replaced with another amino acid residue from the same side chain family.

Recombinant Synthesis

Chemokines, chemokine fragments, or chemokine analogs may also be synthesized, in whole or in part, by recombinant methods using expression vectors encoding all or part of a chemokine.

Vectors, or preferably expression vectors, may contain a gene encoding a polypeptide of the invention, a functional derivative thereof, or another useful polypeptide. These vectors may be employed to express the encoded polypeptide in either prokaryotic or eukaryotic cells.

The term “vector” in this application refers to a DNA molecule into which another DNA of interest can be inserted by incorporation into the DNA of the vector. One skilled in the art is familiar with the term. Examples of classes of vectors can be plasmids, cosmids, viruses, and bacteriophage. Typically, vectors are designed to accept a wide variety of inserted DNA molecules and then used to transfer or transmit the DNA of interest into a host cell (e.g., bacterium, yeast, higher eukaryotic cell). A vector may be chosen based on the size of the DNA molecule to be inserted, as well as based on the intended use. For transcription into RNA or transcription followed by translation to produce an encoded polypeptide, an expression vector would be chosen. For the preservation or identification of a specific DNA sequence (e.g., one DNA sequence in a cDNA library) or for producing a large number of copies of the specific DNA sequence, a cloning vector would be chosen. If the vector is a virus or bacteriophage, the term vector may include the viral/bacteriophage coat.

Following entry into a cell, all or part of the vector DNA, including the insert DNA, may be incorporated into the host cell chromosome, or the vector may be maintained extrachromosomally. Those vectors that are maintained extrachromosomally are frequently capable of autonomous replication in a host cell into which they are introduced (e.g., many plasmids having a bacterial origin of replication). Other vectors are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome.

The term “expression vector” refers to a DNA construct which allows one to place a gene encoding a gene product of interest, usually a protein, into a specific location in a vector from which the selected gene product can be expressed by the machinery of the host cell, or alternately, by in vitro expression system. This type of vector is frequently a plasmid, but other forms of expression vectors, such as bacteriophage vectors and viral vectors (e.g., adenoviruses, replication defective retroviruses, and adeno-associated viruses), may be employed. The selection of expression vectors, control sequences, transformation methods, and the like, are dependent on the type of host cell used to express the gene.

Prokaryotic Hosts

Prokaryotic hosts are, in generally, very efficient and convenient for the production of recombinant polypeptides and are, therefore, one type of preferred expression system. Prokaryotes most frequently are represented by various strains of E. coli, but other microbial strains may be used, including other bacterial strains. Recognized prokaryotic hosts include bacteria such as E. coli, Bacillus, Streptomyces, Pseudomonas, Salmonella, Serratia, and the like. However, under such conditions, recombinantly-produced polypeptides will not be glycosylated.

In prokaryotic systems, vectors that contain replication sites and control sequences derived from a species compatible with the host may be used. Preferred prokaryotic vectors include plasmids such as those capable of replication in E. coli (such as, for example, pBR322, ColEl, pSC101, pACYC184, pVX, pUC118, pUC119 and the like). Suitable phage or bacteriophage vectors may include λgt10, λgt11, vectors derived from filamentous bacteriophage such as m13, and the like. Suitable Streptomyces plasmids include p1J101, and streptomyces bacteriophages such as fC31. Bacillus plasmids include pC194, pC221, pT127, and the like. Suitable Pseudomonas plasmids have been reviewed by Izaki. (Jpn. J. Bacteriol. 33:729-742, 1978) and John et al. (Rev. Infect. Dis. 8:693-704, 1986).

To express a protease of the invention (or a functional derivative thereof) in a prokaryotic cell, it is necessary to operably link the sequence encoding the protease of the invention to a functional prokaryotic promoter. Such promoters are either constitutive or inducible promoters, but commonly inducible promoters are used. Examples of constitutive promoters include the int promoter of bacteriophage λ, the bla promoter of the β-lactamase gene sequence of pBR322, and the cat promoter of the chloramphenicol acetyl transferase gene sequence-of pPR325, and the like. Examples of inducible prokaryotic promoters include the major right and left promoters of bacteriophage λ (PL and PR), the trp, recA, lacZ, lacI, and gal promoters of E. coli, the α-amylase and the V-28-specific promoters of B. subtilis, the promoters of the bacteriophages of Bacillus, and Streptomyces promoters. Prokaryotic promoters are reviewed by Glick (Ind. Microbiot: 1:277-282, 1987), Cenatiempo (Biochimie 68:505-516, 1986), and Gottesman (Ann. Rev. Genet. 18:415-442, 1984). Additionally, proper expression in a prokaryotic cell also requires the presence of a ribosome-binding site upstream of the encoding sequence. Such ribosome-binding sites are disclosed, for example, by Gold et al. (Ann. Rev. Microbiol. 35:365-404, 1981).

Fusion Protein

Proteins may be expressed as fusion proteins. Genes for proteins expressed as fusion proteins ligated into expression vectors that add a number of amino acids to a protein encoded and expressed, usually to the amino terminus of the recombinant protein. Such a strategy of producing fusion proteins is usually adopted for three purposes: (1) to assist in the purification by acting as a ligand in affinity purification, (2) to increase the solubility of the product, and (3) to increase the expression of the product. Often, expression vectors for use in fusion protein production, a proteolytic cleavage site is included at the junction of the fusion region and the protein of interest to enable purification of the recombinant protein away from the fusion region following affinity purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase, and may also include trypsin or chymotrypsin. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith, D. B. and Johnson, K. S. (1988) Gene 67:31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

Improving Yield

Maximizing recombinant protein expression in E. coli can be assisted by expressing the protein or fusion protein in a host bacteria with an impaired proteolytic system so as to reduce the post-synthesis degradation of the recombinant protein (Gottesman, S., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 119-128). Another strategy is to alter the mix of codons used in the coding sequence to reflect the usage of the individual codons for each amino acid in the host (e.g., E. coli (Wada et al., (1992) Nucleic Acids Res. 20:2111-2118)). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques and may prove useful for a variety of prokaryotic and eukaryotic expression systems.

Eukaryotic Hosts

Suitable hosts may include eukaryotic cells. Preferred eukaryotic hosts include, for example, yeast, fungi, insect cells, and mammalian cells both in vivo and in tissue culture. Useful mammalian cell hosts include HeLa cells, cells of fibroblast origin such as VERO or CHO-K1, and cells of lymphoid origin and their derivatives. Preferred mammalian host cells include SP2/0 and J558L, as well as neuroblastoma cell lines such as IMR 332, which may provide better capacities for correct post-translational processing. In general, eukaryotic organisms such as yeast provide substantial advantages in that they can also carry out post-translational modifications.

A large number of yeast expression systems may be potentially utilized which incorporate promoter and termination elements from the actively expressed sequences coding for glycolytic enzymes. These expression systems produce in large quantities of proteins when yeast are grown in mediums rich in glucose. Known glycolytic gene sequences can also provide very efficient transcriptional control signals. A number of recombinant DNA strategies exist utilizing strong promoter sequences and high copy number plasmids which can be utilized for production of the desired proteins in yeast. Examples of vectors suitable for expression in S. cerivisae include pYepSec1 (Baldari, et al., (1987) Embo J. 6:229-234), pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88 (Schultz et al., (1987) Gene 54:113-123), pYES2 (InVitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

In another embodiment, the protein of interest may be expressed in insect cells for example the Drosophila larvae. Using insect cells as hosts, the Drosophila alcohol dehydrogenase promoter may be used (Rubin, Science 240:1453-1459, 1988). Additionally, baculovirus vectors can be engineered to express large amounts of the protein of interest in cultured insect cells (e.g., Sf 9 cells)(Jasny, Science 238:1653, 1987; Miller et al., in: Genetic Engineering, Vol. 8, Plenum, Setlow et al., eds., pp. 277-297, 1986). Vectors which may be used include the pAc series (Smith et al. (1983) Mol. Cell Biol. 3:2156-2165) and the pVL series (Lucklow and Summers (1989) Virology 170:31-39).

Plant cells may also be utilized as hosts, and control sequences compatible with plant cells are available, such as the cauliflower mosaic virus 35S and 19S promoters, and nopaline synthase promoter and polyadenylation signal sequences. Furthermore, the protein of interest may be expressed in plants which have incorporated the expression vector into their germ line.

In yet another embodiment, a nucleic acid of the invention may be expressed in mammalian cells using a mammalian expression vector. Possibilities and techniques for expression in mammalian cells has recently been summarized (Colosimo, et al., “Transfer and expression of foreign genes in mammalian cells,” Biotechniques 29(2):314-8, 320-2, 324 passim, 2000; which is hereby incorporated by reference in its entirety including any drawings, tables, and figures.). Examples of mammalian expression vectors include pCDM8 (Seed, B. (1987) Nature 329:840) and pMT2PC (Kaufinan et al. (1987) EMBO J. 6:187-195). For use in mammalian cells, the regulatory sequences of the expression vector are often derived from viral regulatory elements. For example, commonly used promoters are derived from Simian Virus 40 (SV40), polyoma, Adenovirus 2, and cytomegalovirus (CMV) viruses. Preferred eukaryotic promoters include, for example, the promoter of the mouse metallothionein I gene sequence (Hamer et al., J. Mol. Appl. Gen. 1:273-288, 1982); the TK promoter of Herpes virus (McKnight, Cell 31:355-365, 1982); the SV40 early promoter (Benoist et al., Nature (London) 290:304-31, 1981); and the yeast gal4 gene sequence promoter (Johnston et al., Proc. Natl. Acad. Sci. (USA) 79:6971-6975, 1982; Silver et al., Proc. Natl. Acad. Sci. (USA) 81:5951-5955, 1984). Alternatively, promoters from mammalian expression products, such as actin, collagen, myosin, and the like, may be employed. Regulatory elements may also be derived from adenovirus, bovine papilloma virus, cytomegalovirus, simian virus, or the like.

Transcriptional initiation regulatory signals may be selected which allow for repression or activation, so that expression of the gene sequences can be modulated. Of interest are regulatory signals which are temperature-sensitive so that by varying the temperature, expression can be repressed or initiated, or are subject to chemical (such as metabolite) regulation. Expression of proteins of interest in eukaryotic hosts requires the use of eukaryotic regulatory regions. Such regions will, in general, include a promoter region sufficient to direct the initiation of RNA synthesis.

The recombinant mammalian expression vector may also be designed to be capable of directing expression of the nucleic acid preferentially in a particular cell type (i.e., tissue-specific regulatory elements are used to control the expression). Such tissue-specific promoters include the liver-specific albumin promoter (Pinkert et al. (1987) Genes Dev. 1:268-277); lymphoid-specific promoters (e.g., Calame and Eaton (1988) Adv. Immunol. 43:235-275), and in particular promoters of immunoglobulins and T cell receptors (Winoto and Baltimore (1989) EMBO J. 8:729-733, Banerji et al. (1983) Cell 33:729-740; Queen and Baltimore (1983) Cell 33:741-748); mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166); and pancreas-specific promoters (Edlund et al. (1985) Science 230:912-916). Developmentally-regulated promoters may also be utilized, for example, the α-fetoprotein promoter (Campes and Tilghman (1989) Genes Dev. 3:537-546), and the murine hox promoters (Kessel and Gruss (1990) Science 249:374-379).

Preferred eukaryotic plasmids include, for example, SV40, BPV, pMAM-neo, pKRC, vaccinia, 2-micron circle, and the like, or their derivatives. Such plasmids are well known in the art (Botstein et al., Miami Wntr. Symp. 19:265-274, 1982; Broach, In: “The Molecular Biology of the Yeast Saccharomyces: Life Cycle and Inheritance,” Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., p. 445-470, 1981; Broach, Cell 28:203-204, 1982; Bollon et al., J. Clin. Hematol. Oncol. 10:39-48, 1980; Maniatis, In: Cell Biology: A Comprehensive Treatise, Vol. 3, Gene Sequence Expression, Academic Press, NY, pp. 563-608, 1980).

Once the vector or nucleic acid molecule containing the construct(s) has been prepared for expression, the DNA construct(s) may be introduced into an appropriate host cell by any of a variety of suitable means, i.e., transformation, transfection, conjugation, protoplast fusion, electroporation, particle gun technology, DEAE-dextran-mediated transfection, lipofection, calcium phosphate-precipitation, direct microinjection, and the like. Suitable methods for transforming or transfecting host cells can be-found in Sambrook, et al. (2001). After the introduction of the vector, recipient cells are grown in a selective medium, which selects for the growth of vector-containing cells. Expression of the cloned gene(s) results in the production of a protein of interest, or fragments thereof.

For other suitable expression systems for both prokaryotic and eukaryotic cells see Sambrook, et al, “Molecular Cloning: A Laboratory Manual,” 3rd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 2001, which is-hereby incorporated by reference in its entirety, including any drawings, figures, and tables.

For transformation of eukaryotic cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Preferred selectable markers include those which confer resistance to drugs, such as G418, hygromycin, neomycin, methotrexate, glyphosate, and bialophos. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding the protein of interest or can be introduced on a separate vector. Cells stably transformed with the introduced nucleic acid can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).

A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) the protein of interest. Accordingly, the invention further provides methods for producing the protein of interest using the host cells of the invention. In one embodiment, the method comprises culturing the host cell into which a recombinant expression vector encoding the protein of interest has been introduced in a suitable medium such that the protein of interest is produced, and may be purified by one skilled in the art.

In some aspects of the chemokine analogs of the invention, the analogs contain a linker, having the denoted structure [linker] (shown in bold), wherein the linker has the following structure: H₂N—Z_A—COOH as defined below.

IL-8 Compounds

In one aspect of this invention, the chemokine analogs contain linear IL-8 analogs of the present invention corresponding to a portion of the N-terminal of IL-8 having the following structures:

IL-8-1(1-15) acid or amide a1) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:9) Cys-Gln-Cys-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a2) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:10) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a3) RNH-Xaa₃-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:11) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a4) RNH-Ser-Xaa₃-Lys-Glu-Leu-Arg- (SEQ ID NO:12) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a5) RNH-Ser-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:13) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ IL-8-1(1-13) acid or amide a6) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:14) Cys-Gln-Cys-Ile-Lys-Thr-Tyr- (OH)NH₂ a7) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:15) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ a8) RNH-Xaa₃-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:16) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ a9) RNH-Ser-Xaa₃-Lys-Glu-Leu-Arg- (SEQ ID NO:17) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ a10) RNH-Ser-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:18) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ IL-8-1(1-11) acid or amide a11) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:19) Cys-Gln-Cys-Ile-Lys-(OH)NH₂ a12) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:20) Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂ a13) RNH-Xaa₃-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:21) Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂ a14) RNH-Ser-Xaa₃-Lys-Glu-Leu-Arg- (SEQ ID NO:22) Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂ a15) RNH-Ser-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:23) Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂

Preferred embodiments of linear IL-8 analogs of the present invention corresponding to a portion of the intemal-region of IL-8 having the following structures:

[A⁹]-IL-8-1(9-33) acid or amide a16) RNH-Ala-Ile-Lys-Thr-Tyr-Ser- (SEQ ID NO:24) Lys-Pro-Phe-His-Pro-Lys-Phe- Ile-Lys-Glu-Leu-Arg-Val-Ile- Glu-Ser-Gly-Pro-His-(OH)NH₂ [A³⁴]-IL-8-1(34-49) acid or amide a17) RNH-Ala-Ala-Asn-Thr-Glu-Ile- (SEQ ID NO:25) Ile-Val-Lys-Leu-Ser-Asp-Gly- Arg-Glu-Leu-(OH)NH₂

Preferred embodiments of linear IL-8 analogs of the present invention corresponding to a portion of the C-terminal of IL-8 having the following structures:

IL-8-1(51-72) acid or amide a18) RHN-Leu-Asp-Pro-Lys-Glu-Asn- (SEQ ID NO:26) Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-Ser-(OH)NH₂

Preferred embodiments of linear IL-8 analogs of the present invention corresponding to a portion of the N-terminal joined with a linker to the C-terninal region of IL-8 having the following structures:

IL-8-1(1-15)-[linker]-IL-8-(56-71)-acid or amide a19) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:27) Cys-Gln-Cys-Ile-Lys-Thr-Tyr- Ser-Lys-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a20) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:28) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a22) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:29) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a23) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:30) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Thr-Tyr-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn- (OH)NH₂ a24) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:31) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a25) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:32) Xaa₁-Gln-Xaa₂-Xaa₂-Lys-Thr- Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a26) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:33) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a27) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:34) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a28) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:35) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a29) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:36) Xaa₁-Gln-Xaa₂-Ile-Xaa₄-Thr- Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a30) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:37) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a31) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:38) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a32) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:39) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₁- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a33) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:40) Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄- Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a34) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:41) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a35) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:42) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a36) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:43) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a37) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:44) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Xaa₄-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a38) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:45) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a39) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:46) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a40) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:47) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a41) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:48) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Xaa₄-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a42) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:49) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a43) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:50) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a44) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:51) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a45) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:52) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Ser-Xaa₄-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a46) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:53) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-(OH)NH₂ a47) RNH-Ser-Xaa₃-Lys-Glu-Leu-Ar- (SEQ ID NO:54) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Ser-Xaa₄-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a48) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:55) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ IL-8-1(1-13)-[linker]-IL-8-(56-71)-acid or amide a49) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:56) Cys-Gln-Cys-Ile-Lys-Thr-Tyr- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a50) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:57) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-[linker]-Asn-Trp-Val- Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a51) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:58) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a52) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:59) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a53) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:60) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a54) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:61) Xaa₁-Gln-Xaa₂-Xaa₁-Lys-Thr- Tyr-[linker]-Asn-Trp-Val- Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a55) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:62) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a56) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:63) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a57) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:64) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a58) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:65) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a59) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:66) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a60) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:67) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a61) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:68) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a62) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:69) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a63) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:70) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a64) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:71) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a65) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:72) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a66) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:73) Xaa₁-Gln-Xaa₂--Ile-Lys-Thr- Xaa₁-[linker]-Asn-Trp-Val- Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a67) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:74) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a68) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:75) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a69) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:76) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ IL-8-1(1-11)-[linker]-IL-8-(56-71)-acid or amide a70) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:77) Cys-Gln-Cys-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a71) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:78) Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a72) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:79) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a73) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:80) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a74) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:81) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a75) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:82) Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a76) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:83) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- linker]-Asn-Trp-Val-Gln-Arg- Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a77) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:84) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- linker]-Asn-Trp-Val-Gln-Arg- Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a78) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:85) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- linker]-Asn-Trp-Val-Gln-Arg- Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a79) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:86) Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a80) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:87) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a81) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:88) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a82) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:89) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the-present invention corresponding to a cyclic portion of the N-terminal-region of IL-8 having the following structures:

[Xaa₅¹, Xaa₆¹³]-IL-8-1(1-13) cyclic (Xaa₅-Xaa₆) acid or amide a83) RNH-Xaa₅-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:90) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₆- (OH)NH₂ a84) RNH-Xaa₅-Xaa₃-Lys-Glu-Leu-Arg- (SEQ ID NO:91) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₆- (OH)NH₂ a85) RNH-Xaa₅-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:92) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₆- (OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the present invention corresponding to a cyclic portion of the internal-region of IL-8 having the following structures (the underlined residues below are cyclized):

[Xaa₅⁹, Xaa₆³⁴]-IL-8-1(9-34) cyclic (Xaa₅-Xaa₆) acid or amide a86) RNH-Xaa₅-Ile-Lys-Thr-Tyr-Ser- (SEQ ID NO:93) Lys-Pro-Phe-His-Pro-Lys-Phe- Ile-Lys-Glu-Leu-Arg-Val-Ile- Glu-Ser-Gly-Pro-His-Xaa₆- (OH)NH₂ [Xaa₅³⁴, Xaa₆⁵⁰]-IL-8-1(34-50) cyclic (Xaa₅-Xaa₆) acid or amide a87) RNH-Xaa₅-Ala-Asn-Thr-Glu-Ile- (SEQ ID NO:94) Ile-Val-Lys-Leu-Ser-Asp-Gly- Arg-Glu-Leu-Xaa₆-(OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the present invention corresponding to a cyclic portion of the C-termninal region of IL-8 having the following structures (the underlined residues below are cyclized):

[Xaa₅⁵⁰, Xaa₆⁷²]-IL-8-1(50-72) cyclic (Xaa₅-Xaa₆) acid or amide a88) RNH-Xaa₅-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:95) Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-Xaa₆-(OH)NH₂ [A⁵⁰]-IL-8-1(50-72) cyclic (Glu63-Lys67) acid or amide a89) RHN-Ala-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:96) Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-Ser-(OH)NH₂ [A⁵⁰]-IL-8-1(50-72) cyclic (Lys67-Glu70) acid or amide a90) RHN-Ala-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:97) Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-Ser-(OH)NH₂ [A⁵⁰]-IL-8-1(50-72) cyclic (Lys64-Glu70) acid or amide a91) RHN-Ala-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:99) Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-Ser-(OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to a cyclic portion of the C-terminal region of IL-8 having the following structures (the underlined residues below are cyclized):

IL-8-1(1-15)-[linker]-IL-8-(56-71)-cyclic (Glu63-Lys67) acid or amide a92) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:100) Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a93) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:101) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg- Ala-Glu-Asn-(OH)NH₂ a94) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:102) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a95) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:103) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a96) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:104) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a97) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:105) Arg-Xaa₁-Gln-Xaa₂-Xaa₄- Lys-Thr-Tyr-Ser-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a98) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:106) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a99) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:107) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a100) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:108) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a101) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:109) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a102) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:110) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a103) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:111) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a104) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:112) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a105) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:113) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a106) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:114) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys [linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a107) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:115) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a108) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:116) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a109) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:117) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a110) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:118) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a111) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:119) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a112) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:120) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a113) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:121) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a114) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:122) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a115) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:123) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a116) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:124) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a117) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:125) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn- (OH)NH₂ a118) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:126) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn- (OH)NH₂ a119) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:127) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn- (OH)NH₂ a120) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:128) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn- (OH)NH₂ IL-8-1(1-13)-[linker]-IL-8-(56-71)-cyclic (Glu63-Lys67) acid or amide a121) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:129) Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a122) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:130) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a123) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:131) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a124) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:132) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a125) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:133) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a126) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:134) Arg-Xaa₁-Gln-Xaa₂-Xaa₄- Lys-Thr-Tyr-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg- Ala-Glu-Asn-(OH)NH₂ a127) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:135) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a128) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:136) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a129) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:137) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a130) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:138) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a131) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:139) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a132) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:140) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a133) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:141) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a134) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:142) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₁-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a135) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:143) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a136) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:144) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a137) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:145) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a138) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:146) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a139) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:147) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a140) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:148) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a141) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:149) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ IL-8-1(1-11)-[linker]-IL-8-(56-71) cyclic (Glu63-Lys67) acid or amide a142 RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:150) Arg-Cys-Gln-Cys-Ile-Lys- linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a143) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:151) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a144) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:152) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a145) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:153) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a146) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:154) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a147) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:155) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a148) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:156) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a149) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:157) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a150) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:158) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a151) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:159) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a152) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:160) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a153) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:161) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a154) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:162) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.
Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.
Xaa₅is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid with functional side chain to allow cyclization with Xaa₆.
Xaa₆is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid with functional side chain to allow cyclization with Xaa₅.
- P* is:
  with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamnic acid, lysine to aspartic acid, Orn to Glu, Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=hydrogen, alkyl, alkenyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_n— wherein n is an integer n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) —(Gly)₄—.

IP-10 Compounds:

Preferred embodiments of linear IP-10 analogs of the present invention corresponding to a portion of N-terminal have the following structures:

IP-10-(1-14) acid or amide b1) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:163) Val-Arg-Cys-Thr-Cys-Ile-Ser- Ile-(OH)NH₂ b2) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr- (SEQ ID NO:164) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b3) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr- (SEQ ID NO:165) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b4) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr- (SEQ ID NO:166) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b5) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃- (SEQ ID NO:167) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b6) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:168) Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b7) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:169) Val-Arg-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-(OH)NH₂ IP-10-(1-17) acid or amide b8) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:170) Val-Arg-Cys-Thr-Cys-Ile-Ser- Ile-Ser-Asn-Gln-(OH)NH₂ b9) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr- (SEQ ID NO:171) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b10) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr- (SEQ ID NO:172) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b11) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr- (SEQ ID NO:173) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b12) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃- (SEQ ID NO:174) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b13) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:175) Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b14) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:176) Val-Arg-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- (OH)NH₂

Preferred embodiments of linear IP-10 analogs of the present invention corresponding to a portion of the internal region of IP-10 having the following structures:

[A¹¹]-IP-10-(11-35) acid or amide b15) RNH-Ala-Ile-Ser-Ile-Ser-Asn- (SEQ ID NO:177) Gln-Pro-Val-Asn-Pro-Arg-Ser- Leu-Glu-Lys-Leu-Glu-Ile-Ile- Pro-Ala-Ser-Gln-Phe-(OH)NH₂

Preferred embodiments of linear IP-10 analogs of the present invention corresponding to a portion of the N-terminal region and the internal region of IP-10 having the following structures:

IP-10-(1-35) acid or amide b16) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:178) Val-Arg-Cys-Thr-Cys-Ile-Ser- Ile-Ser-Asn-Gln-Pro-Val-Asn- Pro-Arg-Ser-Leu-Glu-Lys-Leu- Glu-Ile-Ile-Pro-Ala-Ser-Gln- Phe-(OH)NH₂ b17) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:179) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro- Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala- Ser-Gln-Phe-(OH)NH₂ b18) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:180) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro- Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala- Ser-Gln-Phe-(OH)NH₂ b19) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:181) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro- Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala- Ser-Gln-Phe-(OH)NH₂ b20) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:182) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro- Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala- Ser-Gln-Phe-(OH)NH₂ b21) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:183) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro- Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala- Ser-Gln-Phe-(OH)NH₂ b22) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:184) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro- Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala- Ser-Gln-Phe-(OH)NH₂ b23) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:185) Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-Pro-Val- Asn-Pro-Arg-Ser-Leu-Glu-Lys- Leu-Glu-Ile-Ile-Pro-Ala-Ser- Gln-Phe-(OH)NH₂ b24) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:186) Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-Pro-Val- Asn-Pro-Arg-Ser-Leu-Glu-Lys- Leu-Glu-Ile-Ile-Pro-Ala-Ser- Gln-Phe-(OH)NH₂

Preferred embodiments of linear IP-10 analogs of the present invention corresponding to a portion of the C-terminal region of IP-10 having the following sequence:

IP-10-(53-77) acid or amide b25) RNH-Leu-Asn-Pro-Glu-Ser-Lys- (SEQ ID NO:187) Ala-Ile-Lys-Asn-Leu-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser- Lys-Arg-Ser-Pro-(OH)NH₂

Preferred embodiments of cyclic IP-10 analogs of the present invention corresponding to a portion of the N-termninal region joined with a linker to a cyclic portion of the C-terminal region of IP-10 having the following structures:

IP-10-(1-14)-[linker]-IP-10-(65-77)-acid or amide b26) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:188) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b27) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:189) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b28) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:190) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b29) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:191) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b30) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:192) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b31) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:193) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b32) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:194) Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]- Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser- Pro-(OH)NH₂ b33) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:195) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b34) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:196) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b35) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:197) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b36) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:198) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b37) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:199) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b38) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:200) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b39) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:201) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₅-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b40) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:202) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b41) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:203) XaVal-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b42) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:204) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b43) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:205) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b44) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:206) Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b45) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:207) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b46) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:208) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b47) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:209) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b48) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:210) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₂-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b49) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:211) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b50) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:212) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b51) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:213) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b52) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:214) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b53) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:215) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b54) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:216) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b55) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:217) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b56) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:218) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b57) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:219) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b58) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:220) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b59) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:221) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b60) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:222) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b61) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:223) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ IP-10-(1-14)-[linker]-IP-10-(54-66)-acid or amide b62) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:224) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b63) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:225) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b64) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:226) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b65) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:227) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b66) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:228) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b67) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:229) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b68) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:230) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b69) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:231) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b70) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:232) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b71) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:233) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b72) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:234) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b73) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:235) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b74) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:236) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b75) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:237) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b76) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:238) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b77) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:239) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b78) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:240) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b79) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:241) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b80) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:242) Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b81) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:243) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b82) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:244) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b83) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:245) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b84) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:246) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₂-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b85) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:247) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b86) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:248) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b87) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:249) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b88) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:250) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b89) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:251) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b90) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:252) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b91) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:253) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b92) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:254) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b93) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:255) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b94) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:256) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b95) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:257) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b96) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:258) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b97) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:259) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ IP-10-(1-14)-[linker]-IP-10-(59-71)-acid or amide b98) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:260) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b99) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:261) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b100) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:262) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b101) RNH-Val-Pro Xaa₃-Ser-Arg- (SEQ ID NO:263) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b102) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:264) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b103) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:265) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b104) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:266) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b105) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:267) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b106) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:268) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b107) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:269) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b108) RH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:270) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b109) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:271) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b110) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:272) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b111) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:273) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b112) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:274) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b113) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:275) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b114) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:276) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b115) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:277) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b116) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:278) Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b117) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:279) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b118) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:280) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b119) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:281) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b120) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:282) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b121) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:283) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b122) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:284) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b123) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:285) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b124) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:286) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b125) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:287) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b126) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:288) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b127) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:289) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b128) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:290) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b129) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:291) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b130) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:292) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b131) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:293) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b132) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:294) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b133) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:295) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ IP-10-(1-17)-[linker]-IP-10-(65-77)-acid or amide b134) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:296) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b135) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:297) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b136) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:298) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b137) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:299) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b138) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:300) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b139) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:301) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b140) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:302) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b141) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:303) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b142) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:304) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b143) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:305) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro(OH)NH₂ b144) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:306) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b145) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:307) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b146) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:308) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b147) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:309) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b148) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:310) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₅-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b149) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:311) XaVal-Arg-Xaa₁-Thr-Xaa₂- Xaa₁-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b150) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:312) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b151) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:313) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b152) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:314) Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b153) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:315) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b154) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:316) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b155) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:317) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b156) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:318) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b157) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:319) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b158) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:320) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b159) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:321) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b160) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:322) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b161) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:323) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b162) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:324) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b163) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:325) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b164) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:326) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b165) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:327) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b166) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:328) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b167) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:329) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b168) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:330) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b169) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:331) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b170) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:332) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Xaa₁-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b171) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:333) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b172) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:334) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b173) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:335) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b174) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:336) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b175) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:337) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b176) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:338) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b177) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:339) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b178) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:340) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b170e) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:341) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b171e) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:342) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₁- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b172e) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:343) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b173e) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:344) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b174e) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:345) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b175e) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:346) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b176e) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:347) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b177e) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:348) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b178e) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:349) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₁- [linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ IP-10-(1-17)-[linker]-IP-10-(54-66)-acid or amide b179) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:350) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b180) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:351) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b181) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:352) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b182) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:353) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b183) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:354) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b184) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:355) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b185) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:356) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b186) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:357) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b187) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:358) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b188) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:359) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b189) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:360) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b190) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:361) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b191) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:362) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b192) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:363) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b193) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:364) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b194) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:365) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b195) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:366) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b196) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:367) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b197) RH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:368) Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b198) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:369) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b199) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:370) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b200) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:371) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b201) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:372) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b202) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:373) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b203) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:374) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b204) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:375) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b205) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:376) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b206) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:377) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys(OH)NH₂ b207) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:378) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b208) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:379) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b209) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:380) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b210) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:381) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b211) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:382) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b212) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:383) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b213) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:384) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b214) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:385) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b215) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:386) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b216) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:387) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b217) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:388) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b218) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:389) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b219) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:390) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b220) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:391) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b221) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:392) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b222) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:393) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b223) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:394) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b224) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:395) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b225) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:396) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b226) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:397) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b227) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:398) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b228) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:399) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b229) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:400) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b230) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:401) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b231) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:402) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b232) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:403) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ IP-10-(1-17)-[linker]-IP-10-(59-71)-acid or amide b233) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:404) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Asn-Gln [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b234) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:405) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b235) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:406) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b236) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:407) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b237) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:408) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b238) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:409) Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b239) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:410) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b240) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:411) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b241) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:412) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b242) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:413) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b243) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:414) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b244) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:415) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₁-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b245) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:416) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b246) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:417) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b247) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:418) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b248) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:419) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b249) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:420) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b250) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:421) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b251) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:422) Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b252) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:423) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b253) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:424) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b254) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:425) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b255) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:426) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b256) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:427) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b257) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:428) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b258) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:429) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b259) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:430) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b260) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:431) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b261) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:432) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b262) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:433) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b263) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO 434) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b264) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:435) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b265) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:436) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b266) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:437) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b267) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:438) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b268) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:439) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b269) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:440) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b270) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:441) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b271) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:442) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b272) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:443) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b273) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:444) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b274) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:445) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b275) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:446) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b276) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:447) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b277) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:448) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b278) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:449) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b279) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:450) Thr-Val-Arg-Xaa₁-Th-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b280) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:451) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b281) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:452) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b282) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:453) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b283) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:454) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b284) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:455) Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln- Xaa₄-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala- Val-Ser-Lys-Glu-(OH)NH₂ b285) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:456) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b286) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:457) Thr-Val-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln- Xaa₄-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala- Val-Ser-Lys-Glu-(OH)NH₂

Preferred embodiments of cyclic IP-10 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to a cyclic portion of the C-terminal region of IP-10 having the following structures (underlined residues are cyclized):

IP-10-(1-14)-[linker]-IP-10-(65-77)-cyclic (Glu71- Lys74) acid or amide b287) (SEQ ID NO:458) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b288) (SEQ ID NO:459) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b289) (SEQ ID NO:460) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b290) (SEQ ID NO:461) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b300) (SEQ ID NO:462) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b301) (SEQ ID NO:463) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro(OH)NH₂ b302) (SEQ ID NO:464) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b303) (SEQ ID NO:465) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b304) (SEQ ID NO:466) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys- Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b305) (SEQ ID NO:467) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b306) (SEQ ID NO:468) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b307) (SEQ ID NO:469) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b308) (SEQ ID NO:470) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b309) (SEQ ID NO:471) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b310) (SEQ ID NO:472) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b311) (SEQ ID NO:473) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b312) (SEQ ID NO:474) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b313) (SEQ ID NO:475) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b314) (SEQ ID NO:476) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b315) (SEQ ID NO:477) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b316) (SEQ ID NO:478) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b317) (SEQ ID NO:479) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b318) (SEQ ID NO:480) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b319) (SEQ ID NO:481) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b320) (SEQ ID NO:482) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b321) (SEQ ID NO:483) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b322) (SEQ ID NO:484) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b323) (SEQ ID NO:485) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b324) (SEQ ID NO:486) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b325) (SEQ ID NO:487) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b326) (SEQ ID NO:488) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b327) (SEQ ID NO:489) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b328) (SEQ ID NO:490) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b329) (SEQ ID NO:491) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b330) (SEQ ID NO:492) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b331) (SEQ ID NO:493) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ IP-10-(1-17)-[linker]-IP-10-(65-77)-cyclic (Glu71- Lys74) acid or amide b332) (SEQ ID NO:494) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b333) (SEQ ID NO:495) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b334) (SEQ ID NO:496) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b335) (SEQ ID NO:497) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b336) (SEQ ID NO:498) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b337) (SEQ ID NO:499) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b338) (SEQ ID NO:500) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b339) (SEQ ID NO:501) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b340) (SEQ ID NO:502) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b341) (SEQ ID NO:503) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b342) (SEQ ID NO:504) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b343) (SEQ ID NO:505) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b344) (SEQ ID NO:506) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b345) (SEQ ID NO:507) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b346) (SEQ ID NO:508) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b347) (SEQ ID NO:509) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b348) (SEQ ID NO:510) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b349) (SEQ ID NO:511) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b350) (SEQ ID NO:512) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b351) (SEQ ID NO:513) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b352) (SEQ ID NO:514) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b353) (SEQ ID NO:515) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b354) (SEQ ID NO:516) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b355) (SEQ ID NO:517) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b356) (SEQ ID NO:518) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro (OH)NH₂ b357) (SEQ ID NO:519) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b358) (SEQ ID NO:520) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b359) (SEQ ID NO:521) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b360) (SEQ ID NO:522) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b361) (SEQ ID NO:523) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b362) (SEQ ID NO:524) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b363) (SEQ ID NO:525) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b364) (SEQ ID NO:526) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b365) (SEQ ID NO:527) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b366) (SEQ ID NO:528) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b367) (SEQ ID NO:529) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b368) (SEQ ID NO:530) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b369) (SEQ ID NO:531) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b370) (SEQ ID NO:532) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b371) (SEQ ID NO:533) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val- Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b372) (SEQ ID NO:534) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b373) (SEQ ID NO:535) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b374) (SEQ ID NO:536) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b375) (SEQ ID NO:537) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b376) (SEQ ID NO:538) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b377) (SEQ ID NO:539) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser--Gln-Xaa₄-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b378) (SEQ ID NO:540) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b379) (SEQ ID NO:541) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro(OH)NH₂ b380) (SEQ ID NO:542) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b381) (SEQ ID NO:543) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b382) (SEQ ID NO:544) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala- Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b383) (SEQ ID NO:545) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b384) (SEQ ID NO:546) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b385) (SEQ ID NO:548) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ IP-10-(1-14)-[linker]-IP-10-(54-66)-cyclic(Glu57- Lys62) acid or amide b386) (SEQ ID NO:549) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b387) (SEQ ID NO:550) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b388) (SEQ ID NO:551) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b389) (SEQ ID NO:552) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b400) (SEQ ID NO:553) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b401) (SEQ ID NO:554) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b402) (SEQ ID NO:555) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b403) (SEQ ID NO:556) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b404) (SEQ ID NO:557) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b405) (SEQ ID NO:558) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Xaa₄Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b406) (SEQ ID NO:559) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b407) (SEQ ID NO:560) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b408) (SEQ ID NO:561) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b409) (SEQ ID NO:562) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b410) (SEQ ID NO:563) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b411) (SEQ ID NO:564) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b412) (SEQ ID NO:565) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b413) (SEQ ID NO:566) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b414) (SEQ ID NO:567) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b415) (SEQ ID NO:568) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b416) (SEQ ID NO:569) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b417) (SEQ ID NO:570) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b418) (SEQ ID NO:571) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b419) (SEQ ID NO:572) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b420) (SEQ ID NO:573) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b421) (SEQ ID NO:574) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b422) (SEQ ID NO:575) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b423) (SEQ ID NO:576) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b424) (SEQ ID NO:577) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b425) (SEQ ID NO:578) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b426) (SEQ ID NO:579) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b427) (SEQ ID NO:580) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b428) (SEQ ID NO:581) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b429) (SEQ ID NO:582) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b430) (SEQ ID NO:583) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b431) (SEQ ID NO:584) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser- Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ IP-10-(1-17)-[linker]-IP-10-(54-66)-cyclic(Glu57- Lys62) acid or amide b432) (SEQ ID NO:585) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b433) (SEQ ID NO:586) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys(OH)NH₂ b434) (SEQ ID NO:587) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b435) (SEQ ID NO:588) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b436) (SEQ ID NO:589) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b437) (SEQ ID NO:590) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b438) (SEQ ID NO:591) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b439) (SEQ ID NO:592) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b440) (SEQ ID NO:593) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b441) (SEQ ID NO:594) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b442) (SEQ ID NO:595) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b443) (SEQ ID NO:596) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b444) (SEQ ID NO:597) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b445) (SEQ ID NO:598) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b446) (SEQ ID NO:599) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b447) (SEQ ID NO:600) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b448) (SEQ ID NO:601) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b449) (SEQ ID NO:602) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b450) (SEQ ID NO:603) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b451) (SEQ ID NO:604) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b452) (SEQ ID NO:605) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b453) (SEQ ID NO:606) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b454) (SEQ ID NO:607) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b455) (SEQ ID NO:608) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b456) (SEQ ID NO:609) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b457) (SEQ ID NO:610) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b458) (SEQ ID NO:611) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b459) (SEQ ID NO:612) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b460) (SEQ ID NO:613) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b461) (SEQ ID NO:614) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b462) (SEQ ID NO:615) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b463) (SEQ ID NO:616) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b464) (SEQ ID NO:617) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b465) (SEQ ID NO:618) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b466) (SEQ ID NO:619) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b467) (SEQ ID NO:620) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b468) (SEQ ID NO:621) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b469) (SEQ ID NO:622) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b470) (SEQ ID NO:623) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b471) (SEQ ID NO:624) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b472) (SEQ ID NO:625) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b473) (SEQ ID NO:626) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b474) (SEQ ID NO:627) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b475) (SEQ ID NO:628) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b476) (SEQ ID NO:629) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b477) (SEQ ID NO:630) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn-Pro-Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b478) (SEQ ID NO:631) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b479) (SEQ ID NO:632) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b480) (SEQ ID NO:633) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b481) (SEQ ID NO:634) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b482) (SEQ ID NO:635) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu- Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b483) (SEQ ID NO:636) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b484) (SEQ ID NO:637) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b485) (SEQ ID NO:638) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂

In some embodiments IP-10 analogs were cyclized by etherification between Lys66 and Ser69 (underlined residues are cyclized).

IP-10-(1-14)-[linker]-IP-10-(59-71)-cyclic(Lys66- Ser69) acid or amide b486) (SEQ ID NO:639) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b487) (SEQ ID NO:640) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b488) (SEQ ID NO:641) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b489) (SEQ ID NO:642) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b490) (SEQ ID NO:643) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b491) (SEQ ID NO:644) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b492) (SEQ ID NO:645) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b493) (SEQ ID NO:646) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b494) (SEQ ID NO:647) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu- Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b495) (SEQ ID NO:648) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b496) (SEQ ID NO:649) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b497) (SEQ ID NO:650) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b498) (SEQ ID NO:651) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b499) (SEQ ID NO:652) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b500) (SEQ ID NO:653) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b501) (SEQ ID NO:654) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b502) (SEQ ID NO:655) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b503) (SEQ ID NO:656) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b504) (SEQ ID NO:657) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b505) (SEQ ID NO:658) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b506) (SEQ ID NO:659) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b507) (SEQ ID NO:660) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b508) (SEQ ID NO:661) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b509) (SEQ ID NO:662) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b510) (SEQ ID NO:663) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b511) (SEQ ID NO:664) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b512) (SEQ ID NO:665) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b513) (SEQ ID NO:666) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b514) (SEQ ID NO:667) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b515) (SEQ ID NO:668) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b516) (SEQ ID NO:669) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b517) (SEQ ID NO:670) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b518) (SEQ ID NO:671) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b519) (SEQ ID NO:672) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b520) (SEQ ID NO:673) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b521) (SEQ ID NO:674) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ IP-10-(1-17)-[linker]-IP-10-(59-71)-cyclic(Lys66- Ser69) acid or amide b522) (SEQ ID NO:675) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b523) (SEQ ID NO:676) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b524) (SEQ ID NO:677) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b525) (SEQ ID NO:678) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b526) (SEQ ID NO:679) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b527) (SEQ ID NO:680) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b528) (SEQ ID NO:681) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b529) (SEQ ID NO:682) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b530) (SEQ ID NO:683) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b531) (SEQ ID NO:684) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b532) (SEQ ID NO:685) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b533) (SEQ ID NO:686) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b534) (SEQ ID NO:687) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Glu-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b535) (SEQ ID NO:688) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b536) (SEQ ID NO:689) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b537) (SEQ ID NO:690) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b538) (SEQ ID NO:691) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b539) (SEQ ID NO:692) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b540) (SEQ ID NO:693) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b541) (SEQ ID NO:694) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b542) (SEQ ID NO:695) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b543) (SEQ ID NO:696) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b544) (SEQ ID NO:697) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b545) (SEQ ID NO:698) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b546) (SEQ ID NO:699) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b547) (SEQ ID NO:700) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b548) (SEQ ID NO:701) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b549) (SEQ ID NO:702) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b550) (SEQ ID NO:703) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b551) (SEQ ID NO:704) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b552) (SEQ ID NO:705) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b553) (SEQ ID NO:706) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b554) (SEQ ID NO:707) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b555) (SEQ ID NO:708) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b556) (SEQ ID NO:709) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b557) (SEQ ID NO:710) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b558) (SEQ ID NO:711) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b559) (SEQ ID NO:712) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b560) (SEQ ID NO:713) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b561) (SEQ ID NO:714) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b562) (SEQ ID NO:715) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b563) (SEQ ID NO:716) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b564) (SEQ ID NO:717) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b565) (SEQ ID NO:718) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b566) (SEQ ID NO:719) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b567) (SEQ ID NO:720) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala-Ile-Lys- Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b568) (SEQ ID NO:721) RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b569) (SEQ ID NO:722) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b570) (SEQ ID NO:723) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b571) (SEQ ID NO:724) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b572) (SEQ ID NO:725) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile- Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b573) (SEQ ID NO:726) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b574) (SEQ ID NO:727) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b575) (SEQ ID NO:728) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr- Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.
Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.
- P* is:
  with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, Orn to Glu, Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=hydrogen, alkyl, alkenyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_n— wherein n is an integer n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) 13 (Gly)₄—.

MIP-1α Compounds:

Preferred embodiments of linear MIP-1α analogs of the present invention corresponding to a portion of the N-terminal region of MIP-1α having the following sequence:

MIP-1α-(1-9) acid or amide c1) (SEQ ID NO:729) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Ala-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present invention corresponding to a portion of the internal region of MIP-1α having the following sequences:

[A¹¹]-MIP-1α-(11-31) acid or amide c2) (SEQ ID NO:730) RNH-Ala-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln- Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ MIP-1α-(33-47) acid or amide c3) (SEQ ID NO:731) RNH-Ser-Lys-Pro-Gly-Val-Ile-Phe-Leu-Thr-Tyr-Arg- Ser-Arg-Gln-Val-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present invention corresponding to a portion of the N-terminal and the internal region of MIP-1α having the following structures:

MIP-1α-(1-31) acid or amide c4) (SEQ ID NO:732) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe- Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp- Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c5) (SEQ ID NO:733) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c6) (SEQ ID NO:734) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c7) (SEQ ID NO:735) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c8) (SEQ ID NO:736) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c9) (SEQ ID NO:737) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c10) (SEQ ID NO:738) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c11) (SEQ ID NO:739) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c12) (SEQ ID NO:740) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala- Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present invention corresponding to a portion of the C-terminal region of MIP-1α having the following structures:

MIP-1α-(49-66) acid or amide c13) (SEQ ID NO:741) RNH-Ala-Asp-Pro-Ser-Glu-Glu-Trp-Val-Gln-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present invention corresponding to a portion of the N-terminal region joined with a linker to the C-terminal region of MIP-1α having the following structures:

MIP-1α-(1-14)-[linker]-MIP-1α-(53-66) acid or amide c14) (SEQ ID NO:742) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe- Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c15) (SEQ ID NO:743) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c16) (SEQ ID NO:744) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c17) (SEQ ID NO:745) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c18) (SEQ ID NO:746) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c19) (SEQ ID NO:747) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c20) (SEQ ID NO:748) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c21) (SEQ ID NO:749) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c22) (SEQ ID NO:750) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c23) (SEQ ID NO:751) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c24) (SEQ ID NO:752) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c25) (SEQ ID NO:753) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c26) (SEQ ID NO:754) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c27) (SEQ ID NO:755) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c28) (SEQ ID NO:756) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c29) (SEQ ID NO:757) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c30) (SEQ ID NO:758) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c31) (SEQ ID NO:759) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c32) (SEQ ID NO:760) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c33) (SEQ ID NO:761) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c34) (SEQ ID NO:762) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c35) (SEQ ID NO:763) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c36) (SEQ ID NO:764) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c37) (SEQ ID NO:765) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c38) (SEQ ID NO:766) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c39) (SEQ ID NO:767) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c40) (SEQ ID NO:768) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c41) (SEQ ID NO:769) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c42) (SEQ ID NO:770) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c43) (SEQ ID NO:771) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c44) (SEQ ID NO:772) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c45) (SEQ ID NO:773) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c46) (SEQ ID NO:774) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c47) (SEQ ID NO:775) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c48) (SEQ ID NO:776) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c49) (SEQ ID NO:777) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c50) (SEQ ID NO:778) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c51) (SEQ ID NO:779) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c52) (SEQ ID NO:780) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c53) (SEQ ID NO:781) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c54) (SEQ ID NO:782) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c55) (SEQ ID NO:783) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c56) (SEQ ID NO:784) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c57) (SEQ ID NO:785) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c58) (SEQ ID NO:786) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c59) (SEQ ID NO:787) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

In some preferred embodiments, glutamine (Gln57) of MIP-1α analogs was replaced by lysine (Lys).

MIP-1α-(1-14)-[linker]-[K57]-MIP-1α-(53-66) acid or amide c60) (SEQ ID NO:788) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe- Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c61) (SEQ ID NO:789) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c62) (SEQ ID NO:790) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c63) (SEQ ID NO:791) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c64) (SEQ ID NO:792) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c65) (SEQ ID NO:793) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c66) (SEQ ID NO:794) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c67) (SEQ ID NO:795) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c68) (SEQ ID NO:796) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c69) (SEQ ID NO:797) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c70) (SEQ ID NO:798) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c71) (SEQ ID NO:799) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c72) (SEQ ID NO:800) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c73) (SEQ ID NO:801) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c74) (SEQ ID NO:802) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c75) (SEQ ID NO:803) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c76) (SEQ ID NO:804) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c77) (SEQ ID NO:805) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c78) (SEQ ID NO:806) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c79) (SEQ ID NO:807) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c80) (SEQ ID NO:808) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c81) (SEQ ID NO:809) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c82) (SEQ ID NO:810) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c83) (SEQ ID NO:811) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c84) (SEQ ID NO:812) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c85) (SEQ ID NO:813) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c86) (SEQ ID NO:814) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c87) (SEQ ID NO:815) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c88) (SEQ ID NO:816) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c89) (SEQ ID NO:817) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c90) (SEQ ID NO:818) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c91) (SEQ ID NO:819) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c92) (SEQ ID NO:820) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c93) (SEQ ID NO:821) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c94) (SEQ ID NO:822) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c95) (SEQ ID NO:823) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c96) (SEQ ID NO:824) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c97) (SEQ ID NO:825) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c98) (SEQ ID NO:826) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c99) (SEQ ID NO:827) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c100) (SEQ ID NO:828) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c101 (SEQ ID NO:829) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c102) (SEQ ID NO:830) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c103) (SEQ ID NO:831) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c104) (SEQ ID NO:832) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c105) (SEQ ID NO:833) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

Preferred embodiments of cyclic MIP-1α analogs of the present invention corresponding to a cyclic portion of the internal region of MIP-1α having the following structures:

[A¹⁰]-MIP-1α-(10-32) cyclic (Cys11-Cys32) acid or amide c106) (SEQ ID NO:834) RNH-Ala-Cys-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro- Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-Cys- (OH)NH₂ [A¹⁰,K¹¹,E³²]-MIP-1α-(10-32) cyclic (Lys11-Glu32) acid or amide c107) (SEQ ID NO:835) RNH-Ala-Lys-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro- Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-Glu- (OH)NH₂

Preferred embodiments of cyclic MIP-1α analogs of the present invention corresponding to a portion of the N-terminal region joined with a linker to a cyclic the C-terminal region of MIP-1α having the following structures:

MIP-1α-(1-14)-[linker]-[K⁵⁷]-MIP-1α-(53-66) cyclic (Lys57-Asp61) acid or amide c108) (SEQ ID NO:836) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe- Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c109) (SEQ ID NO:837) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c110) (SEQ ID NO:838) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c111) (SEQ ID NO:839) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c112) (SEQ ID NO:840) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c120) (SEQ ID NO:841) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c121) (SEQ ID NO:842) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c122) (SEQ ID NO:843) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c123) (SEQ ID NO:844) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c124) (SEQ ID NO:845) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c125) (SEQ ID NO:846) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c126) (SEQ ID NO:847) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c127) (SEQ ID NO:848) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c128) (SEQ ID NO:849) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c129) (SEQ ID NO:850) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c130) (SEQ ID NO:851) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c131) (SEQ ID NO:852) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c132) (SEQ ID NO:853) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c133) (SEQ ID NO:854) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c134) (SEQ ID NO:855) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c135) (SEQ ID NO:856) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c136) (SEQ ID NO:857) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c137) (SEQ ID NO:858) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c138) (SEQ ID NO:859) RNH-Ser-Leu-Ala-Xaa₁-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c139) (SEQ ID NO:860) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c140) (SEQ ID NO:861) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c141) (SEQ ID NO:862) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c142) (SEQ ID NO:863) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c143) (SEQ ID NO:864) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c144) (SEQ ID NO:865) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c145) (SEQ ID NO:866) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c146) (SEQ ID NO:867) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c147) (SEQ ID NO:868) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c148) (SEQ ID NO:869) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c149) (SEQ ID NO:870) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c150) (SEQ ID NO:871) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c151) (SEQ ID NO:872) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c152) (SEQ ID NO:873) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe- Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val- Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c153) (SEQ ID NO:874) RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c154) (SEQ ID NO:875) RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c155) (SEQ ID NO:876) RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c156) (SEQ ID NO:877) RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c157) (SEQ ID NO:878) RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c158) (SEQ ID NO:879) RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c159) (SEQ ID NO:880) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c160) (SEQ ID NO:881) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂- Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.
Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.
- P* is:
  with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, Orn to Glu, Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_n— wherein n is an integer n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) —(gly)₄—.

RANTES Compounds

Preferred embodiments of linear RANTES analogs of the present invention corresponding to a portion of the N-terminal region of RANTES having the following structures:

RANTES-(1-9) acid or amide d1) (SEQ ID NO:882) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present invention corresponding to a portion of the internal region of RANTES having the following structures:

[A¹¹]-RANTES-(11-33) acid or amide d2) (SEQ ID NO:883) RNH-Ala-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg- Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys- (OH)NH₂ RANTES-(35-49) acid or amide d3) (SEQ ID NO:884) RNH-Ser-Asn-Pro-Ala-Val-Val-Phe-Val-Thr-Arg-Lys- Asn-Arg-Gln-Val-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present invention corresponding to a portion of the N-terminal and a portion the internal region of RANTES having the following structures:

RANTES-(1-33) acid or amide d4) (SEQ ID NO:885) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His- Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present invention corresponding to a portion of the C-terminal region of RANTES having the following structures:

RANTES-(51-68) acid or amide d5) (SEQ ID NO:886) RNH-Ala-Asn-Pro-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr- Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present invention corresponding to a portion of the N-terminal region joined with a linker to the C-terminal region of RANTES having the following structures:

RANTES-(1-14)-[linker]-RANTES-(54-68) acid or amide d6) (SEQ ID NO:887) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d7) (SEQ ID NO:888) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d8) (SEQ ID NO:889) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d9) (SEQ ID NO:890) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d10) (SEQ ID NO:891) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d11) (SEQ ID NO:892) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d12) (SEQ ID NO:893) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d13) (SEQ ID NO:894) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d14) (SEQ ID NO:895) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d15) (SEQ ID NO:896) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d16) (SEQ ID NO:897) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d17) (SEQ ID NO:898) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d18) (SEQ ID NO:899) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d19) (SEQ ID NO:900) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d20) (SEQ ID NO:901) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d21) (SEQ ID NO:902) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d22) (SEQ ID NO:903) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d23) (SEQ ID NO:904) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d24) (SEQ ID NO:905) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d25) (SEQ ID NO:906) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d26) (SEQ ID NO:907) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d27) (SEQ ID NO:908) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d28) (SEQ ID NO:909) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d29) (SEQ ID NO:910) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d30) (SEQ ID NO:911) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d31) (SEQ ID NO:912) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d32) (SEQ ID NO:913) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d33) (SEQ ID NO:914) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d34) (SEQ ID NO:915) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d35) (SEQ ID NO:916) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d36) (SEQ ID NO:917) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d37) (SEQ ID NO:918) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d38) (SEQ ID NO:919) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d39) (SEQ ID NO:920) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₁-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d40) (SEQ ID NO:921) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d41) (SEQ ID NO:922) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₁-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d42) (SEQ ID NO:923) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d43) (SEQ ID NO:924) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d44) (SEQ ID NO:925) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d45) (SEQ ID NO:926) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂

Preferred embodiments of cyclic RANTES analogs of the present invention corresponding to cyclic a portion of the internal region of RANTES having the following structures:

[Ala¹⁰]-RANTES-(10-34) cyclic(Cys11-Cys34) acid or amide d46) (SEQ ID NO:927) RNH-Ala-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro- Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly- Lys-Cys-(OH)NH₂ [Glu¹⁰]-RANTES-(10-33) cyclic(Glu11-Lys33) acid or amide d47) (SEQ ID NO:928) RNH-Glu-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro- Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly- Lys-(OH)NH₂ [Ala¹⁰]-RANTES-(10-34) cyclic(Glu26-Lys33) acid or amide d48) (SEQ ID NO:929) RNH-Ala-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro- Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly- Lys-(OH)NH₂

Preferred embodiments of cyclic RANTES analogs of the present invention corresponding to the N-terminal region and a cyclic a portion of the internal region of RANTES having the following structures:

RANTES-(1-33) cyclic(Glu26-Lys33) acid or amide d49) (SEQ ID NO:930) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His- Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-(OH)NH₂ d50) (SEQ ID NO:931) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂- Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His- Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-(OH)NH₂

Preferred embodiments of cyclic RANTES analogs of the present invention corresponding to a portion of the N-terminal region joined with a linker to cyclic portion of the C-terminal region of RANTES having the following structures:

RANTES-(1-14)-[linker]-RANTES-(54-68) cyclic (Lys56-Glu60) acid or amide d51) (SEQ ID NO:932) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d52) (SEQ ID NO:933) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d53) (SEQ ID NO:934) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d54) (SEQ ID NO:935) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d55) (SEQ ID NO:936) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d56) (SEQ ID NO:937) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d57) (SEQ ID NO:938) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser(OH)NH₂ d58) (SEQ ID NO:939) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d59) (SEQ ID NO:940) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d60) (SEQ ID NO:941) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg- Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d61) (SEQ ID NO:942) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d62) (SEQ ID NO:943) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d63) (SEQ ID NO:944) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d64) (SEQ ID NO:945) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₁-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d65) (SEQ ID NO:946) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d66) (SEQ ID NO:947) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d67) (SEQ ID NO:948) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d68) (SEQ ID NO:949) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d69) (SEQ ID NO:950) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d70) (SEQ ID NO:951) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d71) (SEQ ID NO:952) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d72) (SEQ ID NO:953) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d73) (SEQ ID NO:954) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d74) (SEQ ID NO:955) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d75) (SEQ ID NO:956) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d76) (SEQ ID NO:957) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d77) (SEQ ID NO:958) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d78) (SEQ ID NO:959) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d79) (SEQ ID NO:960) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d80) (SEQ ID NO:961) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d81) (SEQ ID NO:962) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys- Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu- Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d82) (SEQ ID NO:963) RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d83) (SEQ ID NO:964) RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d84) (SEQ ID NO:965) RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d85) (SEQ ID NO:966) RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d86) (SEQ ID NO:967) RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₁-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d87) (SEQ ID NO:968) RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d88) (SEQ ID NO:969) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d89) (SEQ ID NO:970) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d90) (SEQ ID NO:971) RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁- Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val- Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.
Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.
- P* is:
  with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, Orn to Glu, Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_n— wherein n is an integer n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) —(gly)₄—.

I-309 Compounds

Preferred embodiments of linear I-309 analogs of the present invention corresponding to a portion of the N-terminal region of I-309 having the following structures:

[Ala¹⁰]-I-309-(1-10) acid or amide e1) (SEQ ID NO:972) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala- (OH)NH₂

Preferred embodiments of linear I-309 analogs of the present invention corresponding to a portion of the internal region of I-309 having the following structures:

[Ala¹¹]-I-309-(11-25) acid or amide e2) (SEQ ID NO:973) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-(OH)NH₂ [Ala¹¹]-I-309-(11-33) acid or amide e3) (SEQ ID NO:974) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- (OH)NH₂ [A²⁶]-I-309-(26-48) acid or amide e4) (SEQ ID NO:975) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂

Preferred embodiments of linear I-309 analogs of the present invention corresponding to a portion of the N-terminal region and a portion of the internal region of I-309 having the following structures:

I-309-(1-25) acid or amide e5) (SEQ ID NO:976) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e6) (SEQ ID NO:977) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e7) (SEQ ID NO:978) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e8) (SEQ ID NO:979) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e9) (SEQ ID NO:980) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e10) (SEQ ID NO:981) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e11) (SEQ ID NO:982) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e12) (SEQ ID NO:983) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e13) (SEQ ID NO:984) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e14) (SEQ ID NO:985) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂ e15) (SEQ ID NO:986) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂

Preferred embodiments of linear I-309 analogs of the present invention corresponding to a portion of the C-terminal region of I-309 having the following structures:

[Ala³⁴]-I-309-(34-67) acid or amide e16) (SEQ ID NO:987) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His- (OH)NH₂ [Ala⁴⁹]-I-309-(48-73) acid or amide e17) (SEQ ID NO: 988) RNH-Ala-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-His-Cys-Pro-Ser-Lys-Arg- Lys-(OH)NH₂

Preferred embodiments of linear I-309 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to the C-terminal region of I-309 having the following structures:

I-309-(1-14)-[linker]-I-309-(52-64) acid or amide e18) (SEQ ID NO:989) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e19) (SEQ ID NO:990) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e20) (SEQ ID NO:991) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e21) (SEQ ID NO:992) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e22) (SEQ ID NO:993) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e23) (SEQ ID NO:994) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e25) (SEQ ID NO:995) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e26) (SEQ ID NO:996) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e27) (SEQ ID NO:997) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e28) (SEQ ID NO:998) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e29) (SEQ ID NO:999) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e30) (SEQ ID NO:1000) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e31) (SEQ ID NO:1001) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e32) (SEQ ID NO:1002) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e33) (SEQ ID NO:1003) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e34) (SEQ ID NO:1004) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e35) (SEQ ID NO:1005) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e36) (SEQ ID NO:1006) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e37) (SEQ ID NO:1007) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e38) (SEQ ID NO:1008) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e39) (SEQ ID NO:1009) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e40) (SEQ ID NO:1010) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e41) (SEQ ID NO:1011) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e42) (SEQ ID NO:1012) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e43) (SEQ ID NO:1013) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e44) (SEQ ID NO:1014) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e45) (SEQ ID NO:1015) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e46) (SEQ ID NO:1016) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e47) (SEQ ID NO:1017) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e48) (SEQ ID NO:1018) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e49) (SEQ ID NO:1019) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e50) (SEQ ID NO:1020) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e51) (SEQ ID NO:1021) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e52) (SEQ ID NO:1022) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e53) (SEQ ID NO:1023) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e54) (SEQ ID NO:1024) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e55) (SEQ ID NO:1025) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e56) (SEQ ID NO:1026) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e57) (SEQ ID NO:1027) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e58) (SEQ ID NO:1028) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e59) (SEQ ID NO:1029) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e60) (SEQ ID NO:1030) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e61) (SEQ ID NO:1031) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e62) (SEQ ID NO:1032) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ I-309-(1-17)-[linker]-I-309-(52-64) acid or amide e63) (SEQ ID NO:1033) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e64) (SEQ ID NO:1034) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Gln[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e65) (SEQ ID NO:1035) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e66) (SEQ ID NO:1036) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e67) (SEQ ID NO:1037) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e68) (SEQ ID NO:1038) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e69) (SEQ ID NO:1039) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e70) (SEQ ID NO:1040) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e71) (SEQ ID NO:1041) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e72) (SEQ ID NO:1042) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e73) (SEQ ID NO:1043) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e74) (SEQ ID NO:1044) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e75) (SEQ ID NO:1045) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e76) (SEQ ID NO:1046) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e77) (SEQ ID NO:1047) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e78) (SEQ ID NO:1048) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e79) (SEQ ID NO:1049) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e80) (SEQ ID NO:1050) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e81) (SEQ ID NO:1051) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e82) (SEQ ID NO:1052) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e83) (SEQ ID NO:1053) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e84) (SEQ ID NO:1054) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e85) (SEQ ID NO:1055) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e86) (SEQ ID NO:1056) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e87) (SEQ ID NO:1057) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e88) (SEQ ID NO:1058) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e89) (SEQ ID NO:1059) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e90) (SEQ ID NO:1060) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e91) (SEQ ID NO:1061) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e92) (SEQ ID NO:1062) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e93) (SEQ ID NO:1063) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e94) (SEQ ID NO:1064) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e95) (SEQ ID NO:1065) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e96) (SEQ ID NO:1066) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e97) (SEQ ID NO:1067) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e98) (SEQ ID NO:1068) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e99) (SEQ ID NO:1069) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e100 (SEQ ID NO:1070) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e101) (SEQ ID NO:1071) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e102) (SEQ ID NO:1072) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e103) (SEQ ID NO:1073) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e104) (SEQ ID NO:1074) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e105) (SEQ ID NO:1075) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e106) (SEQ ID NO:1076) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e107) (SEQ ID NO:1077) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e108) (SEQ ID NO:1078) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Xaa₄-Glu-Gln[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e109) (SEQ ID NO:1079) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e110) (SEQ ID NO:1080) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e111) (SEQ ID NO:1081) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e112) (SEQ ID NO:1082) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e113) (SEQ ID NO:1083) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e114) (SEQ ID NO:1084) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e115) (SEQ ID NO:1085) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e116) (SEQ ID NO:1086) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e117) (SEQ ID NO:1087) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e118) (SEQ ID NO:1088) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e119) (SEQ ID NO:1089) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Xaa₄-Gln[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e120) (SEQ ID NO:1090) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e121) (SEQ ID NO:1091) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e122) (SEQ ID NO:1092) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e123) (SEQ ID NO:1093) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e124) (SEQ ID NO:1094) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e125) (SEQ ID NO:1095) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp- Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e126) (SEQ ID NO:1096) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e127) (SEQ ID NO:1097) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e128) (SEQ ID NO:1098) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e129) (SEQ ID NO:1099) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e130) (SEQ ID NO:1100) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e131) (SEQ ID NO:1101) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e132) (SEQ ID NO:1102) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e133) (SEQ ID NO:1103) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e134) (SEQ ID NO:1104) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ [Glu⁵⁷]-I-309-(1-14)-[linker]-[Glu⁵⁷]-I-309- (52-62) acid or amide e135) (SEQ ID NO:1105) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e136) (SEQ ID NO:1106) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e137) (SEQ ID NO:1107) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e138) (SEQ ID NO:1108) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e139) (SEQ ID NO:1109) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e140) (SEQ ID NO:1110) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e141) (SEQ ID NO:1111) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e142) (SEQ ID NO:1112) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e143) (SEQ ID NO:1113) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e144) (SEQ ID NO:1114) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e145) (SEQ ID NO:1115) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e146) (SEQ ID NO:1116) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e147) (SEQ ID NO:1117) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e148) (SEQ ID NO:1118) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e149) (SEQ ID NO:1119) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e150) (SEQ ID NO:1120) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e151) (SEQ ID NO:1121) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e152) (SEQ ID NO:1122) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e153) (SEQ ID NO:1123) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e154) (SEQ ID NO:1124) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e155) (SEQ ID NO:1125) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e156) (SEQ ID NO:1126) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e157) (SEQ ID NO:1127) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e158) (SEQ ID NO:1128) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e159) (SEQ ID NO:1129) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e160) (SEQ ID NO:1130) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e161) (SEQ ID NO:1131) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e162) (SEQ ID NO:1132) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e163) (SEQ ID NO:1133) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e164) (SEQ ID NO:1134) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e165) (SEQ ID NO:1135) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e166) (SEQ ID NO:1136) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e167) (SEQ ID NO:1137) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e168) (SEQ ID NO:1138) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e169) (SEQ ID NO:1139) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e170) (SEQ ID NO:1140) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e171) (SEQ ID NO:1141) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e172) (SEQ ID NO:1142) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e173) (SEQ ID NO:1143) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e174) (SEQ ID NO:1144) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e175) (SEQ ID NO:1145) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e176) (SEQ ID NO:1146) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e177) (SEQ ID NO:1147) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e178) (SEQ ID NO:1148) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Glu⁵⁷]-I-309-(1-17)-[linker]-[Glu⁵⁷]-I-309- (52-62) acid or amide e179) (SEQ ID NO:1149) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e180) (SEQ ID NO:1150) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Gln[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e181) (SEQ ID NO:1151) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e182) (SEQ ID NO:1152) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e183) (SEQ ID NO:1153) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e184) (SEQ ID NO:1154) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e185) (SEQ ID NO:1155) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e186) (SEQ ID NO:1156) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e187) (SEQ ID NO:1157) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e188) (SEQ ID NO:1158) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e189) (SEQ ID NO:1159) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e190) (SEQ ID NO:1160) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e191) (SEQ ID NO:1161) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e192) (SEQ ID NO:1162) RNH-Xaa₃-Ser-Met-Glu-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e193) (SEQ ID NO:1163) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e194) (SEQ ID NO:1164) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e195) (SEQ ID NO:1165) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e196) (SEQ ID NO:1166) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e197) (SEQ ID NO:1167) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e198) (SEQ ID NO:1168) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e199) (SEQ ID NO:1169) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e200) (SEQ ID NO:1170) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e201) (SEQ ID NO:1171) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e202) (SEQ ID NO:1172) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e203) (SEQ ID NO:1173) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e204) (SEQ ID NO:1174) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e205) (SEQ ID NO:1175) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e206) (SEQ ID NO:1176) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e207) (SEQ ID NO:1177) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e208) (SEQ ID NO:1178) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e209) (SEQ ID NO:1179) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e210) (SEQ ID NO:1180) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e211) (SEQ ID NO:1181) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e213 (SEQ ID NO:1182) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e214) (SEQ ID NO:1183) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Ala-Glu-Glu-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e215) (SEQ ID NO:1184) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e216) (SEQ ID NO:1185) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e217) (SEQ ID NO:1186) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e218) (SEQ ID NO:1187) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e219) (SEQ ID NO:1188) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e220) (SEQ ID NO:1189) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e221) (SEQ ID NO:1190) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e222) (SEQ ID NO:1191) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e223) (SEQ ID NO:1192) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e224) (SEQ ID NO:1193) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e225) (SEQ ID NO:1194) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Xaa₄-Glu-Gln[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e226) (SEQ ID NO:1195) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e227) (SEQ ID NO:1196) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e228) (SEQ ID NO:1197) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e229) (SEQ ID NO:1198) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e230) (SEQ ID NO:1199) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e231) (SEQ ID NO:1200) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e232) (SEQ ID NO:1201) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e233) (SEQ ID NO:1202) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e234) (SEQ ID NO:1203) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e235) (SEQ ID NO:1204) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e236) (SEQ ID NO:1205) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Xaa₄-Gln[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e237) (SEQ ID NO:1206) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e238) (SEQ ID NO:1207) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e239) (SEQ ID NO:1208) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e240) (SEQ ID NO:1209) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e241) (SEQ ID NO:1210) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e242) (SEQ ID NO:1211) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e243) (SEQ ID NO:1212) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e244) (SEQ ID NO:1213) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e245) (SEQ ID NO:1214) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e246) (SEQ ID NO:1215) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e247) (SEQ ID NO:1216) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e248) (SEQ ID NO:1217) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e249) (SEQ ID NO:1218) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e250) (SEQ ID NO:1219) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e251) (SEQ ID NO:1220) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present invention corresponding to a cyclic portion of the internal region of I-309 having the following structures:

[Ala²⁶]-I-309-(26-49) cyclic(Glu37-Lys42) acid or amide e252) (SEQ ID NO:1221) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂ [Ala²⁶]-I-309-(26-49) cyclic(Glu37-Lys44) acid or amide e253) (SEQ ID NO:1222) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂ [Ala²⁶]-I-309-(26-49) cyclic(Glu37-Lys47) acid or amide e254) (SEQ ID NO:1223) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present invention corresponding to a cyclic portion of the N-terminal region and the internal region of I-309 having the following structures:

I-309-(1-25) cyclic(Lys1-Glu18) acid or amide e256) (SEQ ID NO:1224) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e257) (SEQ ID NO:1225) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ I-309-(1-25) cyclic(Lys1-Glu20) acid or amide e258) (SEQ ID NO:1226) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e259) (SEQ ID NO:1227) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present invention corresponding to a cyclic portion of the C-terminal region of I-309 having the following structures:

[Ala³⁴]-I-309-(34-67) cyclic(Glu37-Lys44) acid or amide e260) (SEQ ID NO:1228) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His- (OH)NH₂ [Ala³⁴]-I-309-(34-67) cyclic(Glu37-Lys44) acid or amide e261) (SEQ ID NO:1229) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67) cyclic(Glu37-Lys47) acid or amide e262) (SEQ ID NO:1230) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67) cyclic(Glu37-Lys63) acid or amide e263) (SEQ ID NO:1231) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ [Ala³⁴]-I-309-(34-67) cyclic(Glu48-Lys63) acid or amide e264) (SEQ ID NO:1232) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67) cyclic(Lys44-Glu48) acid or amide e265) (SEQ ID NO:1233) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67) cyclic(Lys42-Glu48) acid or amide e266) (SEQ ID NO:1234) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys- Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly- Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to a cyclic portion of the C-terminal region of I-309 having the following structures (underlined residues are cyclized):

[Glu⁵⁷]-I-309-(1-14)-[linker]-[Glu⁵⁷]-I-309- (52-62) cyclic(Glu57-Lys61) acid or amide e267) (SEQ ID NO:1235) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e268) (SEQ ID NO:1236) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e269) (SEQ ID NO:1237) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e270) (SEQ ID NO:1238) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e271) (SEQ ID NO:1239) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e272) (SEQ ID NO:1240) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e273) (SEQ ID NO:1241) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e274) (SEQ ID NO:1242) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e275) (SEQ ID NO:1243) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e276) (SEQ ID NO:1244) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e277) (SEQ ID NO:1245) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu- Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e278) (SEQ ID NO:1246) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e279) (SEQ ID NO:1247) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e280) (SEQ ID NO:1248) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e281) (SEQ ID NO:1249) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e282) (SEQ ID NO:1250) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e283) (SEQ ID NO:1251) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₁-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e284) (SEQ ID NO:1252) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e285) (SEQ ID NO:1253) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e286) (SEQ ID NO:1254) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e287) (SEQ ID NO:1255) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e288) (SEQ ID NO:1256) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e289) (SEQ ID NO:1257) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e290) (SEQ ID NO:1258) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e291) (SEQ ID NO:1259) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e292) (SEQ ID NO:1260) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e293) (SEQ ID NO:1261) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e294) (SEQ ID NO:1262) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e295) (SEQ ID NO:1263) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e296) (SEQ ID NO:1264) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e297) (SEQ ID NO:1265) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e298) (SEQ ID NO:1266) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e299) (SEQ ID NO:1267) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e300) (SEQ ID NO:1268) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e301) (SEQ ID NO:1269) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg- His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e302) (SEQ ID NO:1270) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e303) (SEQ ID NO:1271) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e304) (SEQ ID NO:1272) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e305) (SEQ ID NO:1273) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e306) (SEQ ID NO:1274) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e307) (SEQ ID NO:1275) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e308) (SEQ ID NO:1276) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e309) (SEQ ID NO:1277) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e310) (SEQ ID NO:1278) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Glu⁵⁷]-I-309-(1-17)-[linker]-[Glu⁵⁷]-I-309- (52-62) cyclic(Glu57-Lys61) acid or amide e311) (SEQ ID NO:1279) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e312) (SEQ ID NO:1280) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Gln[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e313) (SEQ ID NO:1281) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e314) (SEQ ID NO:1282) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e315) (SEQ ID NO:1283) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e316) (SEQ ID NO:1284) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e317) (SEQ ID NO:1285) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e318) (SEQ ID NO:1286) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e319) (SEQ ID NO:1287) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e320) (SEQ ID NO:1288) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e321) (SEQ ID NO:1289) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly- Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e322) (SEQ ID NO:1290) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e323) (SEQ ID NO:1291) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e324) (SEQ ID NO:1292) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e325) (SEQ ID NO:1293) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e326) (SEQ ID NO:1294) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e327) (SEQ ID NO:1295) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e328) (SEQ ID NO:1296) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e329) (SEQ ID NO:1297) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e330) (SEQ ID NO:1298) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e331) (SEQ ID NO:1299) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e332) (SEQ ID NO:1300) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e333) (SEQ ID NO:1301) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e334) (SEQ ID NO:1302) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e335) (SEQ ID NO:1303) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e336) (SEQ ID NO:1304) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e337) (SEQ ID NO:1305) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e338) (SEQ ID NO:1306) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e339) (SEQ ID NO:1307) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e340) (SEQ ID NO:1308) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e341) (SEQ ID NO:1309) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e342) (SEQ ID NO:1310) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e343) (SEQ ID NO:1311) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e344) (SEQ ID NO:1312) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e345) (SEQ ID NO:1313) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e346) (SEQ ID NO:1314) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e347) (SEQ ID NO:1315) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e348) (SEQ ID NO:1316) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e349) (SEQ ID NO:1317) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e350) (SEQ ID NO:1318) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e351) (SEQ ID NO:1319) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e352) (SEQ ID NO:1320) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e353) (SEQ ID NO:1321) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e354) (SEQ ID NO:1322) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e355) (SEQ ID NO:1323) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e356) (SEQ ID NO:1324) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Xaa₄-Glu-[linker]-Thr-Val-Gly-Trp-Val- Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e357) (SEQ ID NO:1325) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e358) (SEQ ID NO:1326) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e359) (SEQ ID NO:1327) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e360) (SEQ ID NO:1328) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e361) (SEQ ID NO:1329) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e362) (SEQ ID NO:1330) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e363) (SEQ ID NO:1331) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e364) (SEQ ID NO:1332) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e365) (SEQ ID NO:1333) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e366) (SEQ ID NO:1334) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e367) (SEQ ID NO:1335) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Xaa₄-Gln[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e368) (SEQ ID NO:1336) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e369) (SEQ ID NO:1337) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e370) (SEQ ID NO:1338) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e371) (SEQ ID NO:1339) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e372) (SEQ ID NO:1340) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys- Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e373) (SEQ ID NO:1341) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂- Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp- Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e374) (SEQ ID NO:1342) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e375) (SEQ ID NO:1343) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e376) (SEQ ID NO:1344) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e377) (SEQ ID NO:1345) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e378) (SEQ ID NO:1346) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e379) (SEQ ID NO:1347) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e380) (SEQ ID NO:1348) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e381) (SEQ ID NO:1349) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e382) (SEQ ID NO:1350) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁- Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val- Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.
Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.
- P* is:
  with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, Orn to Glu, or Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_n— wherein n is an integer n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) —(gly)₄—.

MCP-1 Compounds:

Preferred embodiments of linear MCP-1 analogs of the present invention corresponding to a portion of the N-terminal and the internal region of MCP-1 having the following structures:

From the chemokine MCP-1 the following compounds:

Preferred embodiments of linear MCP-1 analogs of the present invention corresponding to a portion of the N-terminal and the internal region of MCP-1 having the following structures:

MCP-1-(1-35) acid or amide g2) (SEQ ID NO:1351) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys- Cys-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g3) (SEQ ID NO:1352) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g4) (SEQ ID NO:1353) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g5) (SEQ ID NO:1354) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g6) (SEQ ID NO:1355) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g7) (SEQ ID NO:1356) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g8) (SEQ ID NO:1357) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g9) (SEQ ID NO:1358) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g10) (SEQ ID NO:1359) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g11) (SEQ ID NO:1360) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g12) (SEQ ID NO:1361) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g13) (SEQ ID NO:1362) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ [Glu¹³]-MCP-1-(1-35) acid or amide g14) (SEQ ID NO:1363) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys- Cys-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g15) (SEQ ID NO:1364) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g16) (SEQ ID NO:1365) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g17) (SEQ ID NO:1366) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g18) (SEQ ID NO:1367) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g19) (SEQ ID NO:1368) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g20) (SEQ ID NO:1369) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g21) (SEQ ID NO:1370) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g22) (SEQ ID NO:1371) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g23) (SEQ ID NO:1372) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g24) (SEQ ID NO:1373) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g25) (SEQ ID NO:1374) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂

Preferred embodiments of linear MCP-1 analogs of the present invention corresponding to a portion of the internal region of MCP-1 having the following structures:

MCP-1-(12-36) acid or amide g26) (SEQ ID NO:1375) RNH-Ala-Lys-Xaa₄-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser- Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser- Ser-Lys-Glu-(OH)NH₂ MCP-1-(37-51) acid or amide g27) (SEQ ID NO:1376) RNH-Pro-Lys-Glu-Ala-Val-Ile-Phe-Lys-Thr-Ile-Val- Ala-Lys-Glu-Ile-(OH)NH₂

Preferred embodiments of linear MCP-1 analogs of the present invention corresponding to a portion of the C-terninal region of MCP-1 having the following structures:

MCP-1-(53-76) acid or amide g28) (SEQ ID NO:1377) RNH-Ala-Asp-Pro-Lys-Gln-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂

Preferred embodiments of linear MCP-1 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to the C-terminal region of MCP-1 having the following structures:

MCP-1-(13-35)-[linker]-MCP-1-(58-76) acid or amide g29) (SEQ ID NO:1378) RNH-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- [linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu- Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(1-14)-[linker]-MCP-1-(58-76) acid or amide g30) (SEQ ID NO:1379) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys- Cys-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g31) (SEQ ID NO:1380) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(1-14)-[linker]-MCP-1-(58-76) acid or amide g32) (SEQ ID NO:1381) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g33) (SEQ ID NO:1382) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g34) (SEQ ID NO:1383) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g35) (SEQ ID NO:1384) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g36) (SEQ ID NO:1385) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g37) (SEQ ID NO:1386) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g38) (SEQ ID NO:1387) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g39) (SEQ ID NO:1388) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g40) (SEQ ID NO:1389) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g41) (SEQ ID NO:1390) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g42) (SEQ ID NO:1391) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g43) (SEQ ID NO:1392) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g44) (SEQ ID NO:1393) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g45) (SEQ ID NO:1394) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g46) (SEQ ID NO:1395) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g47) (SEQ ID NO:1396) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g48) (SEQ ID NO:1397) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g49) (SEQ ID NO:1398) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g50) (SEQ ID NO:1399) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g51) (SEQ ID NO:1400) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g52) (SEQ ID NO:1401) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g53) (SEQ ID NO:1402) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g54) (SEQ ID NO:1403) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g55) (SEQ ID NO:1404) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g56) (SEQ ID NO:1405) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g57) (SEQ ID NO:1406) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g58) (SEQ ID NO:1407) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g59) (SEQ ID NO:1408) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g60) (SEQ ID NO:1409) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g61) (SEQ ID NO:1410) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂

Preferred embodiments of cyclic MCP-1 analogs of the present invention corresponding to a cyclic portion of the N-terminal and the internal region of MCP-1 having the following structures:

[Ala¹¹, Lys¹², Glu³⁶]-MCP-1-(11-36) cyclic(Lys12- Glu36) acid or amide g62) (SEQ ID NO:1411) RNH-Ala-Lys-Xaa₃-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser- Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser- Ser-Lys-Glu-(OH)NH₂ [Ala¹¹, Lys¹², Glu³⁶]-MCP-1-(11-36) cyclic(Lys19- Glu36) acid or amide g63) (SEQ ID NO:1412) RNH-Ala-Lys-Xaa₃-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser- Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser- Ser-Lys-Glu-(OH)NH₂ [Glu¹³]-MCP-1-(1-35) cyclic(Glu13-Lys19) acid or amide g64) (SEQ ID NO:1413) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂

Preferred embodiments of cyclic MCP-1 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to a cyclic portion of the C-terminal region of MCP-1 having the following structures:

MCP-1-(1-14)-[linker]-MCP-1-(58-76) cyclic(Asp65- Lys74) acid or amide g65) (SEQ ID NO:1414) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys- Cys-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g66) (SEQ ID NO:1415) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(13-35)-[linker]-MCP-1-(58-76) cyclic(Asp65- Lys74) acid or amide g67) (SEQ ID NO:1416) RNH-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln- Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- [linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu- Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(1-14)-[linker]-MCP-1-(58-76) cyclic(D65- K74) acid or amide g68) (SEQ ID NO:1417) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g69) (SEQ ID NO:1418) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g70) (SEQ ID NO:1419) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g71) (SEQ ID NO:1420) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g72) (SEQ ID NO:1421) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g73) (SEQ ID NO:1422) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g74) (SEQ ID NO:1423) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g75) (SEQ ID NO:1424) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g76) (SEQ ID NO:1425) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g77) (SEQ ID NO:1426) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met- Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g78) (SEQ ID NO:1427) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g79) (SEQ ID NO:1428) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g80) (SEQ ID NO:1429) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g81) (SEQ ID NO:1430) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr(OH)NH₂ (SEQ ID NO:1431) g82) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ (SEQ ID NO:1432) g83) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ (SEQ ID NO:1433) g84) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g85) (SEQ ID NO:1434) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g86) (SEQ ID NO:1435) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g87) (SEQ ID NO:1436) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g88) (SEQ ID NO:1437) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g89) (SEQ ID NO:1438) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g90) (SEQ ID NO:1439) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g91) (SEQ ID NO:1440) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g92) (SEQ ID NO:1441) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g93) (SEQ ID NO:1442) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g94) (SEQ ID NO:1443) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g95) (SEQ ID NO:1444) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g96) (SEQ ID NO:1445) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g97) (SEQ ID NO:1446) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁- Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser- Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group. p0 Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.

P* is:
with Z=Ar, Ar—OH, alkyl and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, Orn to Glu, or Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=Alkyl, Ar, Ar—OH and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_n— wherein n is an integer n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) —(gly)₄—.

CCL28 Compounds

Preferred embodiments of linear CCL28 analogs of the present invention corresponding to a portion of the N-terminal region of CCL28 having the following structures:

CCL28-(1-7) acid or amide h1) (SEQ ID NO:1447) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-(OH)NH₂ CCL28-(1-26) acid or amide h2) (SEQ ID NO:1448) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu- Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu-Arg- Val-Asn-Met-(OH)NH₂ h3) (SEQ ID NO:1449) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu- Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu-Arg- Val-Asn-Met-(OH)NH₂ h4) (SEQ ID NO:1450) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂ h5) (SEQ ID NO:1451) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂ h6) (SEQ ID NO:1452) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂ h7) (SEQ ID NO:1453) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂ h8) (SEQ ID NO:1454) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂ h9) (SEQ ID NO:1455) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂ h10) (SEQ ID NO:1456) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂

Preferred embodiments of linear CCL28 analogs of the present invention corresponding to a portion of the internal region of CCL28 having the following structures:

CCL28-(10-26) acid or amide h11) (SEQ ID NO:1457) RNH-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu- Leu-Glu-Arg-Val-Asn-Met-(OH)NH₂ CCL28-(27-49) acid or amide h12) (SEQ ID NO:1458) RNH-Arg-Ile-Gln-Arg-Ala-Asp-Gly-Asp-Cys-Asp-Leu- Ala-Ala-Val-Ile-Leu-His-Val-Lys-Arg-Arg-Arg-Ile- (OH)NH₂ CCL28-(50-74) acid or amide h13) (SEQ ID NO:1459) RNH-Val-Ser-Pro-His-Asn-His-Thr-Val-Lys-Gln-Trp- Met-Lys-Val-Gln-Ala-Ala-Lys-Lys-Asn-Gly-Lys-Gly- Asn-Val-(OH)NH₂

Preferred embodiments of linear CCL28 analogs of the present invention corresponding to a portion of the C-terminal region of CCL28 having the following structures:

CCL28-(75-102) acid or amide h14) (SEQ ID NO:1460) RNH-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser- Asn-Arg-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly- His-Lys-Thr-Pro-Tyr-(OH)NH₂

Preferred embodiments of linear CCL28 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to the C-terminal region of CCL28 having the following structures:

CCL28-(1-14)-[linker]-[Asp⁸⁶]-CCL28-(75-88) acid or amide h15) (SEQ ID NO:1461) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu- Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly- Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h16) (SEQ ID NO:1462) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h17) (SEQ ID NO:1463) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h18) (SEQ ID NO:1464) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h19) (SEQ ID NO:1465) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h20) (SEQ ID NO:1466) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h21) (SEQ ID NO:1467) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h22) (SEQ ID NO:1468) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h23) (SEQ ID NO:1469) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h24) (SEQ ID NO:1470) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h25) (SEQ ID NO:1471) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h26) (SEQ ID NO:1472) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h27) (SEQ ID NO:1473) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h28) (SEQ ID NO:1474) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h29) (SEQ ID NO:1475) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h30) (SEQ ID NO:1476) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h31) (SEQ ID NO:1477) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h32) (SEQ ID NO:1478) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h33) (SEQ ID NO:1479) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h34) (SEQ ID NO:1480) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h35) (SEQ ID NO:1481) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h36) (SEQ ID NO:1482) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h37) (SEQ ID NO:1483) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h38) (SEQ ID NO:1484) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h39) (SEQ ID NO:1485) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h40) (SEQ ID NO:1486) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h41) (SEQ ID NO:1487) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h42) (SEQ ID NO:1488) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h43) (SEQ ID NO:1489) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h44) (SEQ ID NO:1490) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h45) (SEQ ID NO:1491) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h46) (SEQ ID NO:1492) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h47) (SEQ ID NO:1493) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h48) (SEQ ID NO:1494) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h49) (SEQ ID NO:1495) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h50) (SEQ ID NO:1496) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h51) (SEQ ID NO:1497) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h52) (SEQ ID NO:1498) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h53) (SEQ ID NO:1499) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h54) (SEQ ID NO:1500) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h55) (SEQ ID NO:1501) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h56) (SEQ ID NO:1502) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h57) (SEQ ID NO:1503) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ CCL28-(1-14)-[linker]-CCL28-(88-102) acid or amide h58) (SEQ ID NO:1504) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h59) (SEQ ID NO:1505) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h60) (SEQ ID NO:1506) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h61) (SEQ ID NO:1507) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h62) (SEQ ID NO:1508) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h63) (SEQ ID NO:1509) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h64) (SEQ ID NO:1510) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h65) (SEQ ID NO:1511) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h66) (SEQ ID NO:1512) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h67) (SEQ ID NO:1513) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h68) (SEQ ID NO:1514) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h69) (SEQ ID NO:1515) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h70) (SEQ ID NO:1516) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h71) (SEQ ID NO:1517) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h72) (SEQ ID NO:1518) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h73) (SEQ ID NO:1519) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h74) (SEQ ID NO:1520) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h75) (SEQ ID NO:1521) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h76) (SEQ ID NO:1522) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h77) (SEQ ID NO:1523) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h78) (SEQ ID NO:1524) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h79) (SEQ ID NO:1525) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h80) (SEQ ID NO:1526) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h81) (SEQ ID NO:1527) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h82) (SEQ ID NO:1528) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h83) (SEQ ID NO:1529) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h84) (SEQ ID NO:1530) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h85) (SEQ ID NO:1531) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h86) (SEQ ID NO:1532) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h87) (SEQ ID NO:1533) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h88) (SEQ ID NO:1534) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h89) (SEQ ID NO:1535) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h90) (SEQ ID NO:1536) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h91) (SEQ ID NO:1537) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h92) (SEQ ID NO:1538) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h93) (SEQ ID NO:1539) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h94) (SEQ ID NO:1540) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h95) (SEQ ID NO:1541) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h96) (SEQ ID NO:1542) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h97) (SEQ ID NO:1543) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h98) (SEQ ID NO:1544) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h99) (SEQ ID NO:1545) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂

Preferred embodiments of cyclic CCL28 analogs of the present invention corresponding to a portion the N-terminal region joined with a linker to a cyclic portion of the C-terminal region of CCL28 having the following structures:

CCL28-(1-14)-[linker]-[Asp⁸⁶]-CCL28-(75-88)- cyclic(Lys82-Asp86) acid or amide h100) (SEQ ID NO:1546) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu- Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly- Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h101) (SEQ ID NO:1547) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h102) (SEQ ID NO:1548) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h103) (SEQ ID NO:1549) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h104) (SEQ ID NO:1550) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h105) (SEQ ID NO:1551) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h106) (SEQ ID NO:1552) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h107) (SEQ ID NO:1553) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h108) (SEQ ID NO:1554) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h109) (SEQ ID NO:1555) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h110) (SEQ ID NO:1556) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h111) (SEQ ID NO:1557) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h112) (SEQ ID NO:1558) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h113) (SEQ ID NO:1559) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h114) (SEQ ID NO:1560) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h115) (SEQ ID NO:1561) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h116) (SEQ ID NO:1562) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h117) (SEQ ID NO:1563) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h118) (SEQ ID NO:1564) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h119) (SEQ ID NO:1565) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h120) (SEQ ID NO:1566) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h121) (SEQ ID NO:1567) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h122) (SEQ ID NO:1568) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h123) (SEQ ID NO:1569) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h124) (SEQ ID NO:1570) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h125) (SEQ ID NO:1571) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h125) (SEQ ID NO:1572) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h126) (SEQ ID NO:1573) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h127) (SEQ ID NO:1574) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h128) (SEQ ID NO:1575) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h129) (SEQ ID NO:1576) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h130) (SEQ ID NO:1577) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h131) (SEQ ID NO:1578) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h132) (SEQ ID NO:1579) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h133) (SEQ ID NO:1580) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h134) (SEQ ID NO:1581) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h135) (SEQ ID NO:1582) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h136) (SEQ ID NO:1583) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h137) (SEQ ID NO:1584) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h138) (SEQ ID NO:1585) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h139) (SEQ ID NO:1586) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h140) (SEQ ID NO:1587) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h141) (SEQ ID NO:1588) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His- Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ CCL28-(1-14)-[linker]-CCL28-(88-102)-cyclic(Glu94- Lys99) acid or amide h142) (SEQ ID NO:1589) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu- Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu- Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h143) (SEQ ID NO:1590) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h144) (SEQ ID NO:1591) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h145) (SEQ ID NO:1592) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h146) (SEQ ID NO:1593) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h147) (SEQ ID NO:1594) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h148) (SEQ ID NO:1595) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h149) (SEQ ID NO:1596) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h150) (SEQ ID NO:1597) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h151) (SEQ ID NO:1598) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h152) (SEQ ID NO:1599) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h153) (SEQ ID NO:1600) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h154) (SEQ ID NO:1601) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h155) (SEQ ID NO:1602) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h156) (SEQ ID NO:1603) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄- Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h157) (SEQ ID NO:1604) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h158) (SEQ ID NO:1605) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h159) (SEQ ID NO:1606) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h160) (SEQ ID NO:1607) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h161) (SEQ ID NO:1608) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h162) (SEQ ID NO:1609) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h163) (SEQ ID NO:1610) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h164) (SEQ ID NO:1611) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h165) (SEQ ID NO:1612) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h166) (SEQ ID NO:1613) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h167) (SEQ ID NO:1614) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h168) (SEQ ID NO:1615) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h169) (SEQ ID NO:1616) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h170) (SEQ ID NO:1617) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h171) (SEQ ID NO:1618) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h172) (SEQ ID NO:1619) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h173) (SEQ ID NO:1620) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h174) (SEQ ID NO:1621) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h175) (SEQ ID NO:1622) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h176) (SEQ ID NO:1623) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h177) (SEQ ID NO:1624) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h178) (SEQ ID NO:1625) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h179) (SEQ ID NO:1626) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h180) (SEQ ID NO:1627) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h181) (SEQ ID NO:1628) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h182) (SEQ ID NO:1629) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h183) (SEQ ID NO:1630) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h184) (SEQ ID NO:1631) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr- Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His- Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂

In the above structures:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.
Xaa₃is selected from the group consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and non-natural amino acid.
Xaa₄is selected from the group consisting of P* , Btd and any L- or D-natural amino acid and any non-natural amino acid.
- P* is:
  with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, Orn to Glu, or Orn to Asp. Moieties other than naturally occurring amino acids may also be substituted, such as Btd:

- Btd* is:
- Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, aryl-hydroxy, and more
Xaa₁is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa₂is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminal and C-terminal portions of the analog having the structure: H₂N—Z_A—COOH wherein Z_Ais selected from the group consisting of: (1) alkyl, alkenyl, aralkyl, and alkynyl; (2) —(CH₂)_n— wherein n is an integer, n=9 to 14; (3) any combination of four natural amino acids or non-natural amino acids; and (4) —(gly)₄—.

Compositions

The invention further provides pharmaceutical compositions containing chemokine receptor agonists or antagonists. In one embodiment, such compositions include a chemokine analog compound in a therapeutically, diagnostically or prophylactically effective amount sufficient to be used in treating diseases or disorders selected from the group consisting of autoimmune diseases, acute chronic inflammation, cancer, cardiovascular disease, infectious disease, and inflammatory disorders including rheumatoid arthritis, chronic inflammatory bowel disease, chronic inflammatory pelvic disease, multiple sclerosis, asthma, osteoarthritis, atherosclerosis, psoriasis, rhinitis, autoimmunity, and organ transplant rejection. In another embodiment, such compositions include a chemokine analog compound in a therapeutically or prophylactically effective amount sufficient to be used to increase the hemocrit, assist in mobilizing and recovering stem cells, stimulate the production of blood cells, assist in vaccine production, or assist in gene therapy.

An “effective amount” of a compound of the invention includes a therapeutically effective amount or a prophylatically effective amount. A “therapeutically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired therapeutic result. The term “therapeutically effective amount” may also refer to that amount of active compound, prodrug or pharmaceutical agent that elicits a biological or medicinal response in a tissue, system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician in order to provide a therapeutic effect.

A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result, such as preventing or inhibiting a cytotoxic effect of a cytotoxic agent. Typically, a prophylactic dose is used in organisms prior to or at an earlier stage of disease, so that a prophylactically effective amount may be less than a therapeutically effective amount. The term “preventing” refers to decreasing the probability that an organism contracts or develops an abnormal condition.

In particular embodiments, a preferred range for therapeutically or prophylactically effective amounts of chemokine analogs may be 0.1 nM-0.1 M, 0.1 nM-0.05 M, 0.05 nM-15 μM or 0.01 nM-10 μM. It is to be noted that dosage values may vary with the severity of the condition to be alleviated. For any particular subject, specific dosage regimens may be adjusted over time according to the individual need and the professional judgement of the person administering or supervising the administration of the compositions. Dosage ranges set forth herein are exemplary only and do not limit the dosage ranges that may be selected by medical practitioners.

The amount of active compound in the composition may vary according to factors such as the disease state, age, sex, and weight of the individual. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, a single bolus may be administered, several divided doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It may be advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. “Dosage unit form” as used herein refers to physically discrete units suited as unitary dosages for subjects to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such an active compound for the treatment of sensitivity in individuals.

The terms “administration” or “administering” refer to a method of incorporating a compound into the cells or tissues of an animal, preferably a mammal, and still more preferably a human, in order to treat or prevent an abnormal condition. When the compound or prodrug of the invention is provided in combination with one or active agents, the terms “administration” or “administering” include sequential or concurrent introduction of the compound or prodrug with the other agent(s). For cells harbored within the organism, many techniques exist in the art to administer compounds, including (but not limited to) oral, injection, parenteral, dermal, and aerosol applications.

The term “therapeutic effect” refers to the inhibition or activation of factors causing or contributing to the abnormal condition (including a disease or disorder). A therapeutic effect relieves or prevents to some extent one or more of the symptoms of the abnormal condition. In reference to the treatment of abnormal conditions, a therapeutic effect can refer to one or more of the following: (a) an increase or decrease in the number of lymphocytic cells present at a specified location, (b) an increase or decrease in the ability of lymphocytic cells to migrate, (c) an increase or decrease in the response of lymphocytic cells to a stimulus, (d) an increase or decrease in the proliferation, growth, and/or differentiation of cells; (e) inhibition (i.e., slowing or stopping) or acceleration of cell death; (f) relieving, to some extent, one or more of the symptoms associated with an abnormal condition; (g) enhancing or inhibiting the function of the affected population of cells; (h) activating an enzyme activity present in cells associated with the abnormal condition; and (i) inhibiting an enzyme activity present in cells associated with the abnormal condition.

The term “abnormal condition” refers to a function in the cells or tissues of an organism that deviates from their normal functions in that organism and includes, but is not limited to, conditions commonly referred to as diseases or disorders. An abnormal condition can relate to cell proliferation, cell differentiation, cell survival, cell migration or movement, or the activities of enzymes within a cell. Diseases and disorders may include inflammatory disorders including rheumatoid arthritis, chronic inflammatory bowel disease, chronic inflammatory pelvic disease, multiple sclerosis, asthma, osteoarthritis, atherosclerosis, psoriasis, rhinitis, autoimmunity, organ transplant rejection, and genetic diseases.

As used herein “pharmaceutically acceptable carrier” or “excipient” includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. In one embodiment, the carrier is suitable for parenteral administration. Alternatively, the carrier can be suitable for intravenous, intraperitoneal, intramuscular, sublingual or oral administration. Pharmaceutically acceptable carriers include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the pharmaceutical compositions of the invention is contemplated. Supplementary active compounds can also be incorporated into the compositions. Pharmaceutically acceptable carrier “may comprise pharmaceutically acceptable salts.”

Pharmaceutical formulations for parenteral administration may include liposomes. Liposomes and emulsions are well known examples of delivery vehicles or carriers that are especially useful for hydrophobic drugs. Depending on biological stability of the therapeutic reagent, additional strategies for protein stabilization may be employed. Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with target-specific antibody. The liposomes will bind to the target protein and be taken up selectively by the cell expressing the target protein.

Therapeutic compositions typically must be sterile and stable under the conditions of manufacture and storage. The composition can be formulated as a solution, microemulsion, liposome, or other ordered structure suitable to high drug concentration. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, monostearate salts and gelatin. Moreover, the chemokine analogs may be administered in a time release formulation, for example in a composition which includes a slow release polymer. The active compounds can be prepared with carriers that will protect the compound against rapid release, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanihydrides, polyglycolic acid, collagen, polyorthoesters, polylactic acid and polylactic, polyglycolic copolymers (PLG). Many methods for the preparation of such formulations are patented or generally known to those skilled in the art.

Additionally, suspensions of the compounds of the invention may be prepared as appropriate oily suspensions for injection. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil; or synthetic fatty acid esters, such as ethyl oleate or triglycerides; or liposomes. Suspensions to be used for injection may also contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.

Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. In accordance with an alternative aspect of the invention, a chemokine analog may be formulated with one or more additional compounds that enhance the solubility of the chemokine analog.

If the compounds of the invention are to be administered by inhalation, they may be conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, together with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of gelatin, for example, for use in an inhaler may be formulated containing a powder mix of the compound and a suitable powder base such as starch or lactose.

The term “modulates” refers to altering the function or activity of a chemokine receptor by contacting it with a chemokine or chemokine analog and thus increasing or decreasing the probability that a complex forms between the receptor and a natural binding partner. A chemokine or chemokine analog preferably increases the probability that such a complex forms between the chemokine receptor and the natural binding partner, more preferably increases or decreases the probability that a complex forms between the chemokine receptor and the natural binding partner depending on the concentration of the chemokine or chemokine analog exposed to the receptor, and most preferably decreases the probability that a complex forms between the chemokine receptor and the natural binding partner depending on the concentration of the chemokine or chemokine analog exposed to the polypeptide.

The term “chemokine receptor” refers to a chemokine receptor as the term is used by one skilled in the art and also refers to any other polypeptide capable of binding a chemokine or chemokine analog.

In preferred embodiments, a modulator preferably activates the catalytic activity of a chemokine receptor, more preferably activates or inhibits the catalytic activity of a chemokine receptor depending on the concentration of the chemokine or chemokine analog exposed to the chemokine receptor, or most preferably inhibits the catalytic activity of a chemokine receptor depending on the concentration of the chemokine or chemokine analog exposed to the chemokine receptor.

The term “natural binding partner” refers to G proteins, polypeptides, lipids, small molecules, or nucleic acids that bind to chemokine receptors in cells or in the extracellular environment. The term natural binding partner includes a substrate to be acted upon by the chemokine receptor. A change in the interaction between a chemokine receptor and a natural binding partner can manifest itself as an increased or decreased probability that the interaction forms, or an increased or decreased concentration of chemokine receptor/natural binding partner complex. This can result in a decreased or increased activity of the chemokine receptor.

The terms “activated,” “activating,” and “activation” refer to an increase in the cellular or extracellular function of a chemokine receptor. The chemokine receptor function is preferably the interaction with a natural binding partner, and most preferably catalytic activity. The term “inhibits” refers to decreasing the cellular or extracellular activity of the chemokine receptor. The cellular or extracellular activity of a chemokine receptor is preferably the interaction with a natural binding partner, and most preferably catalytic activity.

The term “complex” refers to an assembly of at least two molecules bound to one another. A signal transduction complex often contains at least two protein molecules bound to one another. For instance, a protein tyrosine receptor protein kinase, GRB2, SOS, RAF, and RAS assemble to form a signal transduction complex in response to a mitogenic ligand. Another example is a chemokine bound to a chemokine receptor. Still another example is a G protein bound to a chemokine receptor.

The term “contacting” as used herein refers to adding together a solution or a composition comprising the chemokine or chemokine analog with a liquid medium bathing the polypeptide or cells comprising a chemokine receptor. The solution comprising the chemokine or chemokine analog may also comprise another component, such as dimethyl sulfoxide (DMSO), which facilitates the uptake of the chemokine or chemokine analog into the cells of the methods. The solution comprising the chemokine or chemokine analog may be added to the medium bathing the cells by utilizing a delivery apparatus, such as a pipette-based device or syringe-based device.

As discussed supra, compounds of the present invention may prove useful in increasing the hemocrit, mobilizing stem cells, or in assisting in vaccine production or otherwise stimulating the immune system to effectuate tumor destruction. For example, the chemokine SDF-1 has been shown to enhance platelet production (Lane et al., Blood 96:4152-59, 2000) and B-cell production (Nagasawa, T., Int. J. Hematol. 72:408-11, 2000), inter alia. Analogs of chemokines may also be useful in improving the engraftment of stem cells following transplantation (Nagasawa, 2000). Chemokine analogs of the invention may also prove useful in mobilizing stem cells (Gazitt, Y., J. Hematother Stem Cell Res 10:229-36, 2001; Hattori et al., Blood 97:3354-59, 2001). They may also prove useful in enhancing anti-tumor immunity (Nomura et al., Int. J. Cancer 91:597-606, 2001; Mach and Dranoff, Curr. Opin. Immunol. 12:571-75, 2000). Other aspects and roles of modulating chemokine function are reviewed in Schwarz and Wells (Schwarz and Wells, Nat. Rev. Drug Discov. 1:347-58, 2002). Chemokine analogs of the present invention may also prove useful in facilitating gene therapy. Glimm and colleagues reported that one chemokine, SDF-1, arrests hematopoietic stem cell cycling, thus allowing a better transfection of these cells with gene constructs for the purpose of gene therapy (Glimm H. et al., “Ex vivo treatment of proliferating human cord blood stem cells with stroma-derived factor-1 enhances their ability to engraft NOD/SCID mice,” Blood 99(9):3454-57, 2002). All of the above references are incorporated by reference herein their entirety, including any drawings, tables, and figures.

EXAMPLES

The following examples illustrate, but do not limit, the present invention.

Example 1

The efficacy of chemokine analogs of the invention as chemokine receptor agonists is demonstrated through receptor binding assays. A competitive dose response for binding to a chemokine receptor by the natural binding chemokine, another chemokine, and chemokine analogs of the invention may be demonstrated by the method set forth in Daugherty et al., Methods in Molecular Biology v138 “Chemokine Protocols” edited by Proudfoot et al., Human Press, Totowa, N.J. p129-148, 2000, which is hereby incorporated by reference in its entirety, including any figures, tables and drawings.

Example 2

The efficacy of chemokine analogs of the invention as chemokine receptor agonists is demonstrated through chemotaxis assays. The effect of a native chemokine and chemokine analogs of the invention may be compared by the method set forth in Ponath et al., Methods in Molecular Biology v138 “Chemokine Protocols” edited by Proudfoot et al., Human Press, Totowa, N.J. p113-120, 2000, which is hereby incorporated by reference in its entirety, including any figures, tables and drawings.

Example 3

(IL-8)

The efficacy of IL-8 and IL-8 peptide analogs as CXCR1 and CXCP2 agonists was demonstrated through CXCR1 and CXCR2 receptor binding assays. A competitive dose response for binding to the IL-8 receptor by native IL-8 and the CXCR1 and CXCR2 agonists against ¹²⁵I-IL-8 is shown in FIG. 1. THP-1 cells, a human monocytoid cell line, were preincubated with the IL-8 or IL-8 analogs for 30 min, then were assessed for ¹²⁵I-IL-8 binding following 2 hr of incubation with ¹²⁵I-IL-8. 10nM ¹²⁵I-IL-8 was added in the presence of IL-8 and the indicated analogs (competing ligands) at the concentrations illustrated. The results are expressed as percentages of the maximal specific binding that was determined without competing ligand. A concentration-dependent inhibition of ¹²⁵I-IL-8 is illustrated, indicating the affinity of IL-8 for the receptor. The inhibition of ¹²⁵I-IL-8 by IL-8 and the IL-8 analogs is indicative of CXCR1 and CXCR2 receptor binding. The compounds illustrated in the figure are as follows: IL-8, Compounds A, B, and C.

Compound A (SEQ ID NO:1632) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-Ser-Lys-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂. Compound B (SEQ ID NO:1633) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂. Compound C (SEQ ID NO:1634) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys- [Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂.

Example 4

(I-309)

This example illustrates the efficacy of I-309 peptide analogs in mediating intracellular calcium mobilization ([Ca²+]_i). To illustrate that the binding of I-309 peptide analogs results in the agonistic activation of the CCR8 receptor, [Ca²+]_imobilization assays were conducted, the results of which are shown in FIG. 2. To obtain the data shown in FIG. 2, Fluo-4,AM loaded human peripheral blood mononuclear cells (PBMC), at 5×10⁶cells/ml, were stimulated with Compounds D, E, F, G and H at the concentrations indicated. The values represent the mean+/−one S.D. As shown by the data in FIG. 2, incubation of PBMC with Compounds E, F and G resulted in the receptor-mediated induction of [Ca²+]_imobilization.

Compound D: (SEQ ID NO:1635) H₂N-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala-NH₂. Compound E: (SEQ ID NO:1636) H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-NH₂. Compound F: (SEQ ID NO:1637) H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- NH₂. Compound G: (SEQ ID NO:1638) H₂N-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-NH₂. Compound H: (SEQ ID NO:1639) H₂N-Ala-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-His-Cys-Pro-Ser-Lys-Arg- Lys-(OH)NH₂.

Example 5

Peptides of the invention may be synthesized chemically using the Fmoc/tBu strategy on a continuous flow peptide synthesizer, as for example has been carried out using the following protocols:

Reagents (solvents, support, chemicals)

Main Solvent: N,N-Dimethylformamide (DMF): certified ACS spectroanalyzed from Fisher (D131-4) M. W=73.10. The DMF is treated with activated molecular sieves, type 4A (from BDH: B54005) for at least two weeks then tested with FDNB (2,4-Dinitrofluorobenzene from Eastman).

Procedure: Mix equal volumes of FDNB solution (1 mg/ml in 95% EtOH) and DMF; Let stand 30 minutes; read the absorbance at 381 nm over a FDNB blank (0.5 ml FDNB+0.5 ml 95% EtOH). If the absorbance˜0.2, the DMF is suitable to be used for the synthesis.

Deblocking Agent: 20% Piperidine (from Aldrich Chemical company, catalog No: 10,409-4) in DMF containing 0.5 % Triton X100 v/v ( from Sigma, catalg No: T-9284).

Activating Agents: 2-(H-benzotriazol-1 yl) 1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU: M. W.=321.09. from Quantum Richilieu, catalog No: R0139)/Hydroxybenzotriazole (HOBt M. W.=135.1 from Quantum Richilieu, catalog No.: R0166-100) respectively, 0.52 M in DMF and 4-Methylmorpholine (NMM; M. W.=101.15, d=0.926 from Aldrich, catalog No.: M5,655-7): 0.9 M in DMF or in the case of sensitive amino acids to racemization like Cys, we use 2,4,6-Collidine, 99% ( M. W.=121.18, d=0.917, from Aldrich, catalog No: 14,238-7): 0.78M in DMF/DCM, 1/1 v/v.

Support: TentaGel R RAM (90 μm), RinK-type Fmoc (from Peptides International, catalog No.: RTS -9995-PI): 0.21 mmol/g, 0.5 g for 0.1 mmol of peptide.

Fmoc-L-amino derivative, side-chains protected with: Boc; tBu; Trt groups: with 4 fold excess (from Peptides International, Bachem, Novabiochem, Chem-Impex Inc). Glu24 and Lys24 are Allyl-protected (from Millipore/Perseptive Biosystems).

Initial Amino Loading and Peptide Synthesis Procedure

The first amino acid Asn31 and the remaining residues are double coupled at room temp. or at 45° C. automatically with 4-fold excess in each coupling. The synthesis is interrupted after residue Leu19. The peptide-bound support is removed from the synthesizer column and placed in a react-vial containing a small magnetic bar for gentle stirring.

Removal of The Allyl Groups

A solution of tetrakis(triphenylphosphine)Palladium(0) Pd(PPh3)4 (from Sigma-Aldrich, catalog No: 21,666-6); M. W.=1155.58×0.1 mmol peptide×3 fold=347 mg dissolved in 5% Acetic Acid; 2.5% NMM in CHC13 to 0.14 M, under argon. The solution is added to the support-bound peptide previously removed from the coulmn in a reactvial containing a small mangnetic bar for gentle stirring. The mixture is flushed with argon, sealed and stirred at room temperature for 6 hours. The support-bound peptide is transferred to a filter funnel, washed with 30 ml of a solution made of 0.5% Sodium Diethyldithiocarbonate/in DMF, then DCM; DCM/DMF (1:1) and DMF. A positive Kaiser test indicate the deprotection of the amino side. chaine of the Lys20.

Lactam Formation:

Activating agent: 7-Azabenztriazol-1-yloxytris (pyrrolindino) phosphonium-hexafluorophosphate (PyAOP: M. W.=521.7 from PerSeptive Biosystems GmbH, catalog No: GEN076531), 1.4-fold: 0.105 mmol×1.4×521.7=76.6 mg and NMM 1.5-fold: 0.105×1.4×1.5=0.23 mmol v=0.23/0.9 M NMM solution=263 μl).

The cyclisation may be carried out in an amino acid vial at room temperature overnight (˜16 hours) with gentle agitation. The completion of cyclization may be indicated by a negative kaiser test. The support-bound peptide may be poured into the column, washed with DMF and the synthesis continues to completion, with a cyclic amide bridge thereby introduced into the peptide.

Final Product Removal From The Support:

The support-bound peptide is removed from the synthesizer in to a medium filter funnel, washed with DCM to replace the non-volatile DMF and thoroughly dried under high vacuum for at least two hours, or preferably, overnight.

Cleavage Mixture (Reagent K):

TFA/Phenol/Water/Thio-Anisol/EDT (82/5/5/5/2.5); 7.5 ml

Support: 0.5 g resin-peptide.

TFA 6.15 ml (Biograde from Halocarbon) Phenol 0.375 ml (Aldrich) Water 0.375 ml (MillQ) Thio-Anisol 0.375 ml (Aldrich) EDT 0.187 ml (Aldrich) Total 7.5 ml

The cleavage may be performed at room temperature for 4 hours with gentle agitation on a rocker.

Precipitation of the Peptide

The cleaved peptide solution is filtered through a filter funnel in a 50 ml round bottom flask. The support is rinsed twice with 4 ml TFA. The TFA solution is concentrated on a rotavap and added drop wise into a cold diethyl ether previously treated with activated neutral aluminum oxide to make it free of peroxide. Approximately 10-fold excess of ether are used. The beads are stored until the yield is determined and peptide characterized. The precipitate is collected at room temperature in screw capped 50 ml polypropylene vial by centrifugation at 2K rpm using a top bench centrifuge (4 minutes run time). The pellet is washed 3×with cold ether, centrifuged and dried with a flow of argon. The precipitate is dissolved in 20% acetonitrile, 0.1% TFA and lyophilized.

Crude Product Characterization:

The product is characterized by analytical HPLC.

Experimental conditions: Column: Vydac 218TP54: C18 reversed-phase 5 μm, 4.6 mm ID×150 mm L.
Eluants: 0.1% TFA/H₂O (solvant A); 0.1% TFA/acetonitrile (solvent B).
Elution Conditions: 20-50% B (40 min); 60-90% B (5 min); 90-20% B (5 min); 20% B (10 min). At 1.0 ml/min and A214 nm=0.5 absorbance unit full scale.
Sample Preparation:

An aliquot of the product is weighed and dissolved in 20% acetonitrile 0.1% TFA at a concentration of 2 mg/ml. The solution is microfuged and 20μl is applied onto the column. The main peak or the major peaks are collected, SpeedVac dried and molecular weight determined by mass spectrometry.

Structure of some of the compounds used in this study is shown below.

Compound A or a19 (SEQ ID NO:27), wherein R═H, Xaa₁=Cys, Xaa₂=Cys, [linker]=4* Gly):

(SEQ ID NO:1632) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-Ser-Lys-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂.

Compound B or a49 (SEQ ID NO:56), wherein R═H, Xaa₁=Cys, Xaa₂=Cys, [linker]=4* Gly):

(SEQ ID NO:1633) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂.

Compound C or a70 (SEQ ID NO:77), wherein R═H, Xaa₁=Cys, Xaa₂=Cys, [linker]=4* Gly):

(SEQ ID NO:1634) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys- [Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂.

Compound D or el (SEQ ID NO:972), wherein R═H):

(SEQ ID NO:1635) H₂N-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala-NH₂.

Compound E or e2 (SEQ ID NO:973), wherein R═H)

(SEQ ID NO:1636) H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-NH₂.

Compound F or e3 (SEQ ID NO:974), wherein R═H):

(SEQ ID NO:1637) H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- NH₂.

Compound G or e4 (SEQ ID NO:975), wherein R═H):

(SEQ ID NO:1638) H₂N-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-NH₂.

Compound H or e17 (SEQ ID NO:988), wherein R═H):

(SEQ ID NO:1639) H₂N-Ala-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg- His-Arg-Lys-Met-Leu-Arg-His-Cys-Pro-Ser-Lys-Arg- Lys-(OH)NH₂.

The invention illustratively described herein can suitably be practiced in the absence of any element or elements, limitation or limitations that is not specifically disclosed herein. Thus, for example, the terms “comprising,” “including,” “containing,” etc., shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalent of the invention shown or portion thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modifications and variations of the inventions embodied herein disclosed can be readily made by those skilled in the art, and that such modifications and variations are considered to be within the scope of the inventions disclosed herein. The inventions have been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form the part of these inventions. This includes within the generic description of each of the inventions a proviso or negative limitation that will allow removing any subject matter from the genus, regardless or whether or not the material to be removed was specifically recited. In addition, where features or aspects of an invention are described in terms of the Markush group, those schooled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group. Further, when a reference to an aspect of the invention lists a range of individual members, as for example, ‘SEQ ID NO:9 to SEQ ID NO:162, inclusive,’ it is intended to be equivalent to listing every member of the list individually, and additionally it should be understood that every individual member may be excluded or included in the claim individually.

The steps depicted and/or used in methods herein may be performed in a different order than as depicted and/or stated. The steps are merely exemplary of the order these steps may occur. The steps may occur in any order that is desired such that it still performs the goals of the claimed invention.

From the description of the invention herein, it is manifest that various equivalents can be used to implement the concepts of the present invention without departing from its scope. Moreover, while the invention has been described with specific reference to certain embodiments, a person of ordinary skill in the art would recognize that changes can be made in form and detail without departing from the spirit and the scope of the invention. The described embodiments are considered in all respects as illustrative and not restrictive. It should also be understood that the invention is not limited to the particular embodiments described herein, but is capable of many equivalents, rearrangements, modifications, and substitutions without departing from the scope of the invention. Thus, additional embodiments are within the scope of the invention and within the following claims.

Further, all patents and publications described herein are hereby incorporated by reference to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.

Claims

1.-11. (canceled)

12. An I-309 mimetic comprising an N-terminal region and a C-terminal region, wherein the I-309 mimetic has a total of about 10 to about 34 amino acid residues, and

the N-terminal region comprises a conserved amino acid sequence selected from a group consisting of SEQ ID NO:972, variant, e1, and conservative amino acid substitutions thereof, and has the following general structure:

(SEQ ID NO:972) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala- (OH)NH2;

wherein, R is an N-terminal modifier comprising a component selected from a group consisting of a hydrogen, a poly(ethylene glycol) or derivative thereof, a diagnostic label, an acyl group, an acetyl group, and a modifier capable of reducing the ability of the I-309 mimetic to act as a substrate for aminopeptidases; and, the (OH)NH2 is a hydroxy or amine group that comprises the C-terminal region or attaches to any combination of up to 7 additional amino acid residues that attach to a linker that attaches to the C-terminal region, wherein the C-terminal region consists of amino acid residues 52-64 of SEQ ID NO:5; and,

the linker is (1) H2N—ZA—COOH, wherein ZA is selected from the group consisting of saturated and unsaturated aliphatics consisting of 20 or fewer carbon atoms that are optionally substituted with a hydroxyl, carboxyl, carbonyl, thiol, amino, amido, imino, or aromatic group having from 5 to 7 members in the ring; and —(CH2)n—, wherein n is an integer ranging from 9 to 14; or (2) any combination of four natural amino acids.

13. The compound of claim 12, wherein the linker is 11-aminoundecanoic acid.

14. The composition of claim 12, wherein R comprises a poly(ethylene glycol), a glycosaminoglycan, or derivative thereof, each having a molecular weight of less than about 20,000 Daltons.

15. The composition of claim 12, wherein the conserved amino acid sequence is selected from a group consisting of SEQ ID NO:1635 and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:1635) H2N-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala-NH2.

16. The composition of claim 12, wherein the conserved amino acid sequence composes the first 10 amino acid residues of the I-309 mimetic.

17. The composition of claim 12, wherein the C-terminal region is cyclized at Glu57 and Lys61.

18. The composition of claim 12, wherein the I-309 mimetic is selected from a group consisting of SEQ ID NO:972, variant e1, and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:972) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala- (OH)NH2;

19. An I-309 mimetic comprising an N-terminal region and a C-terminal region, wherein the I-309 mimetic has a total of about 15 to about 25 amino acid residues, and the N-terminal region or C-terminal region comprises a conserved amino acid sequence selected from a group consisting of SEQ ID NO:973, variant e2, and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:973) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-(OH)NH2; wherein, R is an N-terminal region or an N-terminal modifier comprising a component selected from a group consisting of a hydrogen, a poly(ethylene glycol) or derivative thereof, a diagnostic label, an acyl group, an acetyl group, and a modifier capable of reducing the ability of the I-309 mimetic to act as a substrate for aminopeptidases; and, the (OH)NH2 is a hydroxy or amine group that comprises the C-terminal region, or attaches to any combination of additional amino acid residues composing the C-terminal region; and, the I-309 mimetic consists essentially of the conserved amino acid sequence and from 0 to 10 additional amino acid residues of any combination.

20. The composition of claim 19, wherein R comprises a poly(ethylene glycol), a glycosaminoglycan, or derivative thereof, each having a molecular weight of less than about 20,000 Daltons.

21. The composition of claim 19, wherein the conserved amino acid sequence is selected from a group consisting of SEQ ID NO:1636 and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:1636) H2N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-NH2.

22. The composition of claim 19, wherein the conserved amino acid sequence composes the first 15 amino acid residues of the I-309 mimetic.

23. The composition of claim 19, wherein the conserved amino acid sequence is selected from a group consisting of SEQ ID NO:974, variant e3, and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:974) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- (OH)NH2.

24. The composition of claim 19, wherein the I-309 mimetic is selected from a group consisting of SEQ ID:1637 and conservative amino acid substitutions thereof, and has the following structure: (SEQ ID NO:1637) H2N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- NH2.

25. The composition of claim 19, wherein the I-309 mimetic is selected from a group consisting of SEQ ID NO:973, variant e2, and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:973) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-(OH)NH2.

26. The composition of claim 19, wherein the I-309 mimetic is selected from a group consisting of SEQ ID NO:974, variant e3, and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:974) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- (OH)NH2.

27. An I-309 mimetic comprising an N-terminal region and a C-terminal region, wherein the N-terminal region or C-terminal region comprises a conserved amino acid sequence selected from a group consisting of SEQ ID NO:975, variant e4, and conservative amino acid substitutions thereof, and has the following general structure: (SEQ ID NO:975) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn- Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH2; wherein, R is an N-terminal modifier comprising a component selected from a group consisting of a hydrogen, a poly(ethylene glycol) or derivative thereof, a diagnostic label, an acyl group, an acetyl group, and a modifier capable of reducing the ability of the I-309 mimetic to act as a substrate for aminopeptidases; and, the (OH)NH2 is a hydroxy or amine group that comprises the C-terminal region, or attaches to any combination of additional amino acid residues composing the C-terminal region; and, the I-309 mimetic consists essentially of the conserved amino acid sequence and from 0 to 10 additional amino acid residues of any combination.

28. The composition of claim 27, wherein R comprises a poly(ethylene glycol), a glycosaminoglycan, or derivative thereof, each having a molecular weight of less than about 20,000 Daltons.

29. A method of increasing an I-309-mediated activity of a cell having an I-309 receptor comprising binding the I-309 receptor of the cell with the I-309 mimetic of claim 13.

30. A method of increasing an I-309-mediated activity of a cell having an I-309 receptor comprising binding the I-309 receptor of the cell with the I-309 mimetic of claim 20.

31. A method of increasing an I-309-mediated activity of a cell having an I-309 receptor comprising binding the I-309 receptor of the cell with the I-309 mimetic of claim 28.