Novel chemokine mimetics synthesis and their use

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The present disclosure generally teaches compositions comprising SDF-1 mimetics and methods of using them to modulate an activity of a cell having an SDF-1 receptor by binding the SDF-1 receptor to an SDF-1 mimetic. The cell can be a hematopoietic cell, for example, and can be selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils. In some embodiments, the activity can include the rate of multiplication of the cell or, where the cell is a quiescent cell, the binding can repress the activation of the quiescent cell. Other embodiments of the present invention are taught herein.

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Description
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of prior U.S. application Ser. No. 10/222,703, filed Aug. 16, 2002, which is a continuation-in-part of prior U.S. application Ser. No. 10/086,177, filed Feb. 26, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/835,107, filed Apr. 12, 2001, which claims the benefit of provisional U.S. Application No. 60/232,425, filed Apr. 12, 2001; U.S. application Ser. No. 10/086,177 claims the benefit of U.S. provisional Application Nos. 60/373,628, filed Apr. 17, 2002, and 60/373,629, filed Apr. 17, 2002; and each of these prior applications, specifically enumerated above, is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

This invention relates to the preparation, design, derivation, and use of peptide agonists and antagonists of the chemokine SDF-1. In one aspect, this invention also relates to the preparation, design, or use of chemokine analogs for human SDF-1 or SDF-1/MIP-1α hybrids, or derivatives thereof.

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 cysteines and between the second and fourth cysteines. 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 the four cysteine motif is lymphotactin, which has only two cysteine residues. Thus, lymphotactin retains 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.

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.

MIP-1α

Macrophage inflammatory protein-1α (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-1-alpha may also act to inhibit stem cell proliferation.

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 autoimmune responses. They also play a very important role in normal homeostasis, including lymphoid development and migration. Further, they play a role in the growth of bones. As a result of their role in various physiological processes and pathological conditions and diseases, chemokines have many 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)

Certain agonists of CXCR4 have been described in International Publication No. WO 01/76615 A2 entitled “CXCR4 Agonist Treatment of Hematopoietic Cells” (PCT/CA01/00540). Certain antagonists of CXCR4 have been described in International Publication No. WO 01/85196 A2 entitled “CXCR4 Antagonist Treatment of Hematopoietic Cells” (PCT/CA01/00659. Both PCT publications are hereby incorporated by reference herein, including any drawings, figures and tables.

SUMMARY OF THE INVENTION

The embodiments of the present invention generally encompass compositions comprising SDF-1 mimetics and methods of using them to modulate an activity of a cell having an SDF-1 receptor. In some embodiments, the methods comprise binding the SDF-1 receptor of the cell with an SDF-1 mimetic consisting of the following structure:

RN-HN-Xaa3-Pro-Val-Ser-Leu-Ser- (SEQ ID NO: 10). Tyr-Arg-Xaa1-Pro-Xaa2-Arg-Phe- Phe-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu- Asn-RC

RN can be an N-terminal modifier that comprises a component selected from a group consisting of hydrogen, poly(ethylene glycol), a biochemical label, a radiolabel, an acyl group, an acetyl group, and an N-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for aminopeptidases. RC can be a C-terminal modifier that comprises a component selected from a group consisting of a hydroxyl group, poly(ethylene glycol), a biochemical label, a radiolabel, an amido group, and a C-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for carboxypeptidases. The Xaa1, Xaa2, and Xaa3 variables can be each independently selected from a group consisting of (a) any natural amino acid; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, where ZA is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms, cycloalkyl amines, and fused cycloalkyl amines. The linker can be selected from a group consisting of (a) any combination of four natural amino acids; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, wherein ZA is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms that are optionally substituted with a hydroxyl, carboxyl, carbonyl, thiol, amino, amido, imino, or an aromatic group having from 5 to 7 members in the ring; and —(CH2)n—, wherein n is an integer ranging from 9 to 14.

The cell can be a hematopoietic cell selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils. In some embodiments, the binding can reduce the rate of multiplication of the cell or, where the cell is a quiescent cell, the binding can repress the activation of the quiescent cell.

In some embodiments, the invention is a method of modulating an activity of hematopoietic cells in a subject comprising administering an effective amount of a composition comprising the SDF-1 mimetic to the subject. In these embodiments, the administering can result in mobilizing the hematopoietic cells; and enhancing recovery of the hematopoietic cells following chemotherapy, such as by reducing the rate of multiplication of the hematopoietic cells to inhibit the effect of a cytotoxic agent on the hematopoietic cells during the chemotherapy. In some embodiments, the administering can result in enhancing an engraftment of the hematopoietic cells from the subject in a second subject. In some embodiments, the method further comprises administering a second agent, wherein the administering of the second agent is sequential or concurrent to the administering of the composition comprising the SDF-1 mimetic. In these embodiments, the second agent can include G-CSF.

In some embodiments, the invention includes method of increasing the number of hematopoietic cells circulating in the blood of a subject, wherein the method comprises administering an effective amount of a composition comprising an SDF-1 mimetic.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the induction of [Ca2+]i mobilization by SDF-1 and SDF-1 analogs. Fluo-4,AM loaded SUP-T1 cells (5×106/ml) were stimulated with SDF-1, Compound A (SEQ ID NO:809), Compound B (SEQ ID NO:810), Compound C (SEQ ID NO:811), Compound D (SEQ ID NO:812) and Compound E (SEQ ID NO:813) at the concentrations indicated. The values represent the mean+/−one S.D. of one representative experiment from three independent experiments.

FIG. 2 shows the concentration-dependent inhibition of 125I-SDF-1 binding to CXCR4 by SDF-1, obtained as described, indicating the affinity of SDF-1 for the CXCR4 receptor on SUP-T1 cells, a human lymphoid cell line. FIG. 2 also shows the CXCR4 receptor binding of the SDF-1 peptide analogs (competing ligands described in Example 2). SUP-T1 cells were preincubated with SDF-1 or peptide analogs for 30 min, then were assessed for 125I-SDF-1 binding following 2 hr of incubation with 125I-SDF-1. 0.5 nM 125I-SDF-1 was added in the presence of SDF-1 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, and are the representative results from three independent experiments.

FIG. 3 shows the effect of Ara-C (350 mg/kg) on White Blood Cell Count (WBC) in mice in the presence (triangular data points, solid line, designated Ara-C+Compound A in the legend) and absence (circular data points, dashed line, designated Ara-C in the legend) of a peptide of the invention.

FIG. 4A shows a concentration-dependant inhibition of 125I-SDF-1 binding to CXCR4 by SDF-1, obtained as described for the data shown in FIG. 4A, indicating the affinity of SDF-1 for the CXCR4 receptor. FIG. 4B shows the CXCR4 receptor binding of SDF-1 and the SDF-1 peptide agonist analogs. SDF-1 and the indicated analogs (competing ligands, described in Examples) were added at the concentrations illustrated in the presence of 4 nM 125I-SDF-1. CEM cells were assessed for 125I-SDF-1 binding following 2 hr of incubation. The results are expressed as percentages of the maximal specific binding that was determined without competing ligand, and are the mean of three independent experiments.

FIG. 5 shows the induction of [Ca2+]i mobilization by SDF-1 and SDF-1 receptor analogs (described in Examples). Fura-2,AM loaded THP-1 cells (1×106/ml) were stimulated with SDF-1, Compound A or Compound K at the concentrations indicated. The values represent the mean+/−one S.D. of n=3 experiments.

FIG. 6 shows the induction of [Ca2+]i mobilization by SDF-1 and SDF-1 analogs. Fura-2,AM loaded THP-1 cells (1×106/ml) were stimulated with native SDF-1 and the SDF-1 peptide analogs at the concentration of native SDF-1 concentration that gave the maximum [Ca2+]i stimulation (1 μM). The values represent the mean+/−one S.D. of n=3 experiments. The designated compounds are as follows: SDF-1; Compound A (SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809)); Compound K (SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Glu24/Lys28-cyclic amide (SEQ ID NO:803)); Compound J (SDF-1 (1-9)2-Cys9/Cys9-cysteine dimer (SEQ ID NO:802)); Compound N (SDF-1(1-17) (SEQ ID NO:804)); Compound M/SDF-1 (1-8)2-lysine bridge dimer (SEQ ID NO:805)); and Compound I/SDF-1(1-14)-(G)4-SDF-1(55-67) amide (SEQ ID NO:801).

FIG. 7 shows cyclic proliferative activity of primitive normal colony forming cells (CFC) in the adherent layer of a standard long term culture (LTC), in which circles represent BFU-E cells (burst forming unit-erythroid precursors), and squares represent CFU-GM cells (colony forming unit—granulocyte-monocyte common precursor), illustrating the inhibitory effect of SDF-1 on cellular proliferation as measured by the susceptibility of the cells to an agent preferentially cytotoxic to proliferating cells.

FIG. 8 shows cyclic proliferative activity of primitive normal CFC in the adherent layer of standard LTC, when treated with SDF-1, SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (Compound A (SEQ ID NO:809)), SDF-1(1-9)2 (Compound J (SEQ ID NO:802)), as measured by the susceptibility of the cells to an agent preferentially cytotoxic to dividing cells.

FIG. 9 shows the effect of SDF-1 and SDF-1 analogs (defined in Examples) on the cycling of human progenitors from fetal liver transplanted NOD/SCID mice. The cycling status of mature and primitive colony forming cells (CFU-GM; colony forming unit-granulocyte-monocyte precursor, BFU-E; burst forming unit-erythroid precursor) in the suspension of CD34+ cells isolated from the marrow of transplanted NOD/SCID mice was determined by assessing the proportion of these progenitors that were inactivated (killed) by short term (20 min) or overnight (LTC-IC; long-term culture initiating cell) exposure of the cells to 20 μg/ml of high specific activity 3H-thymidine. Values represent the mean+/−the S.D. of data from up to four experiments with up to four mice per point in each.

FIG. 10 shows data indicating that SDF-1 enhances the detectability of CRU (colony regenerating units) regenerated in NOD/SCID Mice transplanted with human fetal liver.

FIG. 11 shows the effect of SDF-1 and SDF-1 Agonists (defined in Examples) on the engraftment of human cells in human fetal liver transplanted NOD/SCID mice. A comparison of the number of phenotypically defined hematopoietic cells detected in the long bones (tibias and femurs) of mice four weeks after being transplanted with 107 light-density human fetal liver blood cells and then administered SDF-1, Compound A (SEQ ID NO:809) or Compound L (SEQ ID NO:806) (0.5 mg/kg) three times per week for two weeks before sacrifice. Values represent the mean+/−one S.D. of results obtained from three to seven individual mice in three experiments.

FIG. 12 shows the effect of Compound A (SEQ ID NO:809) (1 mg/kg, defined in the Examples) on the recovery of leukocytes following myeloablative chemotherapy with Ara-C (300 mg/kg). Mice were treated with Ara-C alone (Ara-C) or in combination with Compound A. The results represent the mean+/−one S.D. of 6 animals/group.

FIG. 13 shows the effect of Compound A (SEQ ID NO:809) (defined in Examples) and Neupogen® (G-CSF) on the growth of white blood cells in Ara-C treated mice. C3Hhen mice (female) were treated with 500 mg/kg Ara-C for two cycles—on days 0 and 10. During the second cycle of Ara-C dosing, Ara-C treated mice were injected with 10 mg/kg Compound A (SEQ ID NO:809), 10 mg/kg Neupogen®, alone or together (on days −1, 0, and 1 to 3). Control represents animals treated with Ara-C alone. Blood was collected from the tail vein into heparin-containing tubes at the onset of the experiment, and one day before and 1, 7 and 12 days following the second Ara-C dose. A total white blood cell count was obtained. The results represent the mean+/−one S.D. of 6 animals/group.

FIG. 14 shows the effect of Compound A (SEQ ID NO:809) and Neupogen® on the relative growth of white blood cells in Ara-C treated mice. C3Hhen mice (female) were treated with 500 mg/kg Ara-C for two cycles—on days 0 and 10. During the second cycle of Ara-C dosing, Ara-C treated mice were injected with 10 mg/kg Compound A (SEQ ID NO:809) (defined in Examples), 10 mg/kg Neupogen®, alone or together (on days −1, 0, and 1 to 3). Control represents animals treated with Ara-C alone. Blood was collected from the tail vein into heparin-containing tubes at the onset of the experiment, and one day before 7 and 12 days following the second Ara-C dose. A total white blood cell count was obtained. The increase in leukocytes (white blood cells) was determined relative to the number of cells counted the day before the second cycle Ara-C dose was administered. The results represent the mean+/−one S.D. of 6 animals/group.

FIG. 15 shows the amino acid sequences of human SDF-1.alpha, SDF-1 Precursor (PBSF) and SDF-1.beta.

FIG. 16 shows a dose response curve for the mobilization of hematopoietic progenitor cells into the circulation in a mouse following treatment with Compound B (SEQ ID NO:810).

FIG. 17 lists the sequences of several chemokine analogs.

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 that bind to receptors for human SDF-1. In another aspect, the invention is directed to the synthesis, design, derivation, or use of agonist or antagonist analogs of human SDF-1, and derivatives thereof. In a further aspect, the invention is directed to the synthesis, design, derivation, or use of agonist or antagonist analogs of hybrids of human SDF-1 and human MIP-1α, 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 sequence of the human CXC chemokine, SDF-1, is shown below:

SDF-1: (SEQ ID NO:1) Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys-Arg- Phe-Phe-Glu-Ser-His-Val-Ala-Arg-Ala-Asn-Val-Lys- His-Leu-Lys-Ile-Leu-Asn-Thr-Pro-Asn-Cys-Ala-Leu- Gln-Ile-Val-Ala-Arg-Leu-Lys-Asn-Asn-Asn-Arg-Gln- Val-Cys-Ile-Asp-Pro-Lys-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn

The sequence of the CC chemokine, MIP-1α, is shown below:

MIP-1α (SEQ ID NO:2) Ser-Leu-Ala-Ala-Asp-Thr-Pro-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

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. In the native compounds, the beta sheet structure that connects the two termini appears to play a role in the stabilization of the chemokine and assuring that the termini are in the proper conformation.

Examples of these chemokine 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 an amino acid sequence derived from the wild-type chemokine sequence but with one or more of the cysteines replaced with another amino acid. 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 chemokine 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 SDF-1 and MIP-1α.

Chemokine analogs of the invention are useful for treating inflammatory conditions, autoimmune disorders, cancer, vaccine production and blood cell recovery following chemotherapy or stem cell mobilization, as well as graft rejection, bacterial infection, viral infection, vascular conditions (for example, atherosclerosis, restenosis, systemic lupus erythematosis, and ischemia-reperfusion), sepsis, tumorigenesis, and angiogenesis. 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 and multiple sclerosis and other immunological 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 transplant. Examples of uses of the chemokine analogs in some aspects of the invention for vaccine production includes, 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 it may be treated by chemokine analogs of the invention. Chemokine analogs of the present 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 corresponding 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” and “chemokine analogs.” 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. Further, 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:818 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, pp 129-134, Raphaele, B. et al. “Calcium Mobilization,” Methods in Molecular Biology (2000) vol. 138, pp 143-148, Paul D. Ponath et al., “Transwell Chemotaxis,” Methods in Molecular Biology (2000) vol. 138, pp 113-120 Humana Press. Totowa, N.J.). Aspects of biological activity include, but are not limited to, receptor binding, chemotaxis, calcium mobilization, and 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

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.

Modifying Groups

In one aspect of the invention, the chemokine analogs of the invention, such as chemokine analogs derived from SDF-1, 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, analogs or derivatives thereof, which may flank the SDF-1 or MIP-1α core peptidic structure. For example, the modifying group can be coupled to the amino-terminus or carboxy-terminus of a SDF-1 or MIP-1α 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 a SDF-1 or MIP-1α 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 or heterocyclic 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, 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, heterocycles, hydroxyls, aminos, nitros, thiols amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates, selenoethers, ketones, aldehydes, esters, —CF3, —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 atoms.

In one embodiment of the invention, 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 and all or a portion of the carboxy-terminal domain of a chemokine or chemokine analog are connected with a linker. In another embodiment, the 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, 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, and 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, or —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, arylalkyls, 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-C20 for straight chain, C3-C20 for 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), and 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 R7 is alkyl, alkenyl, alkynyl, aryl, aralkyl or heterocyclyl.

The term “amino,” as used herein, refers to —N(Rα)(Rβ), in which Rα and Rβ are each independently hydrogen, alkyl, alkyenyl, alkynyl, aralkyl, aryl, or in which Rα and Rβ 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(Rα)(Rβ), in which Rα and Rβ are as defined above. The term “acylamino” refers to —N(R′α)C(O)—R7, in which R7 is as defined above and R′β 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 a SDF-1-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-acetylneuraminyl group, a trans-4-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, 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 SDF-1 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.

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., Cancer 94(4 Suppl): 1275-86, 2002; Kaltsas et al., 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 plasmon 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, avidin/biotin 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 pharmacokinetics 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 SDF-1 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 chemokine analog of the invention-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 Metathesis) 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 (L or 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.

In some aspects of the chemokine analogs of the invention, the analogs contain a linker, having the denoted structure [linker], wherein the linker has the following structure: H2N-ZA-COOH as defined below.

SDF-1 Compounds:

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

SDF-1(1-14)-[linker]-SDF-1(55-67) acid or amide

f1) (SEQ ID NO:9) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f2) (SEQ ID NO:10) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f3) (SEQ ID NO:11) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f4) (SEQ ID NO:12) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f5) (SEQ ID NO:13) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f6) (SEQ ID NO:14) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f7) (SEQ ID NO:15) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f8) (SEQ ID NO:16) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f9) (SEQ ID NO:17) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f10) (SEQ ID NO:18) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f11) (SEQ ID NO:19) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f12) (SEQ ID NO:20) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-LysTrp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f13) (SEQ ID NO:21) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaas-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f14) (SEQ ID NO:22) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f15) (SEQ ID NO:23) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f16) (SEQ ID NO:24) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f17) (SEQ ID NO:25) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f18) (SEQ ID NO:26) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f19) (SEQ ID NO:27) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f20) (SEQ ID NO:28) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f21) (SEQ ID NO:29) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f22) (SEQ ID NO:30) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f23) (SEQ ID NO:31) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f24) (SEQ ID NO:32) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f25) (SEQ ID NO:33) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-IIe-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f26) (SEQ ID NO:34) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f27) (SEQ ID NO:35) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f28) (SEQ ID NO:36) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f29) (SEQ ID NO:37) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f30) (SEQ ID NO:38) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f31) (SEQ ID NO:39) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f32) (SEQ ID NO:40) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f33) (SEQ ID NO:41) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f34) (SEQ ID NO:42) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f35) (SEQ ID NO:43) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f36) (SEQ ID NO:44) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2

SDF-1(1-17)-[linker]-SDF-1(55-67) amide:

f37) (SEQ ID NO:45) RHN-Lys-Pro-VaI-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f38) (SEQ ID NO:46) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f39) (SEQ ID NO:47) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f40) (SEQ ID NO:48) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f41) (SEQ ID NO:49) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f42) (SEQ ID NO:50) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f43) (SEQ ID NO:51) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f44) (SEQ ID NO:52) RRN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f45) (SEQ ID NO:53) RHN-Lys-Pro-VaI-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f46) (SEQ ID NO:54) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f47) (SEQ ID NO:55) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f48) (SEQ ID NO:56) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f49) (SEQ ID NO:57) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f50) (SEQ ID NO:58) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f51) (SEQ ID NO:59) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f52) (SEQ ID NO:60) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f53) (SEQ ID NO:61) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f54) (SEQ ID NO:62) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f55) (SEQ ID NO:63) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f56) (SEQ ID NO:64) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f57) (SEQ ID NO:65) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f58) (SEQ ID NO:66) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f59) (SEQ ID NO:67) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f60) (SEQ ID NO:68) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f61) (SEQ ID NO:69) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f62) (SEQ ID NO:70) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f63) (SEQ ID NO:71) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f64) (SEQ ID NO:72) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f65) (SEQ ID NO:73) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f66) (SEQ ID NO:74) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f67) (SEQ ID NO:75) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f68) (SEQ ID NO:76) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f69) (SEQ ID NO:77) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f70) (SEQ ID NO:78) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f71) (SEQ ID NO:79) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f72) (SEQ ID NO:80) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f73) (SEQ ID NO:81) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f74) (SEQ ID NO:82) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f75) (SEQ ID NO:83) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f76) (SEQ ID NO:84) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f77) (SEQ ID NO:85) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH) NH2 f78) (SEQ ID NO:86) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f79) (SEQ ID NO:87) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f80) (SEQ ID NO:88) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f80) (SEQ ID NO:89) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-AIa-Leu-Asn- (OH)NH2 f82) (SEQ ID NO:90) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f83) (SEQ ID NO:91) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f84) (SEQ ID NO:92) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f85) (SEQ ID NO:93) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f86) (SEQ ID NO:94) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f87) (SEQ ID NO:95) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f88) (SEQ ID NO:96) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f89) (SEQ ID NO:97) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f90) (SEQ ID NO:98) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f91) (SEQ ID NO:99) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f92) (SEQ ID NO:100) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f93) (SEQ ID NO:101) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f94) (SEQ ID NO:102) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-T4yr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f95) (SEQ ID NO:103) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f96) (SEQ ID NO:104) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f97) (SEQ ID NO:105) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f98) (SEQ ID NO:106) RHN-Lys-Pro-VaI-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f99) (SEQ ID NO:107) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2

Similarly, chemokine analogs may be prepared using sequences from chemokines other than SDF-1. Such as residues 35-49, 10-49, or 55-69 of MP-1α:

SDF-1(1-14)-[linker]-MIP-1α (35-49)-acid or amide

f100) (SEQ ID NO:108) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile-Phe- Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f102) (SEQ ID NO:109) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f103) (SEQ ID NO:110) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f104) (SEQ ID NO:111) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f105) (SEQ ID NO:112) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f106) (SEQ ID NO:113) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f107) (SEQ ID NO:114) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f108) (SEQ ID NO:115) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f109) (SEQ ID NO:116) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile- Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f110) (SEQ ID NO:117) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile-Phe- Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f111) (SEQ ID NO:118) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f112) (SEQ ID NO:119) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f113) (SEQ ID NO:120) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f114) (SEQ ID NO:121) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f115) (SEQ ID NO:122) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f116) (SEQ ID NO:123) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f117) (SEQ ID NO:124) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f118) (SEQ ID NO:125) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f119) (SEQ ID NO:126) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f120) (SEQ ID NO:127) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 (121) (SEQ ID NO:128) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f122) (SEQ ID NO:129) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f123) (SEQ ID NO:130) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f124) (SEQ ID NO:131) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f125) (SEQ ID NO:132) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f126) (SEQ ID NO:133) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- IIe-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f127) (SEQ ID NO:134) RHN-Lys-Pro-VaI-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f128) (SEQ ID NO:135) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val-Ile-Phe- Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f129) (SEQ ID NO:136) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f130) (SEQ ID NO:137) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f131) (SEQ ID NO:138) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f132) (SEQ ID NO:139) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f133) (SEQ ID NO:140) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f134) (SEQ ID NO:141) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f135) (SEQ ID NO:142) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f136) (SEQ ID NO:143) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2

SDF-1(1-14)-[linker]-MIP-1α (55-69)-acid or amide

f137) (SEQ ID NO:144) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f138) (SEQ ID NO:145) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f139) (SEQ ID NO:146) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f140) (SEQ ID NO:147) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f141) (SEQ ID NO:148) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f142) (SEQ ID NO:149) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f143) (SEQ ID NO:150) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f144) (SEQ ID NO:151) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f145) (SEQ ID NO:152) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f146) (SEQ ID NO:153) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f147) (SEQ ID NO:154) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f148) (SEQ ID NO:155) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f149) (SEQ ID NO:156) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f150) (SEQ ID NO:157) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f151) (SEQ ID NO:158) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f152) (SEQ ID NO:159) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f153) (SEQ ID NO:160) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f154) (SEQ ID NO:161) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f155) (SEQ ID NO:162) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f156) (SEQ ID NO:163) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f157) (SEQ ID NO:164) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f158) (SEQ ID NO:165) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f159) (SEQ ID NO:166) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f160) (SEQ ID NO:167) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f161) (SEQ ID NO:168) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f162) (SEQ ID NO:169) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f163) (SEQ ID NO:170) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f164) (SEQ ID NO:171) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f165) (SEQ ID NO:172) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f166) (SEQ ID NO:173) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f167) (SEQ ID NO:174) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f168) (SEQ ID NO:175) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f169) (SEQ ID NO:176) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f170) (SEQ ID NO:177) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f171) (SEQ ID NO:178) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f172) (SEQ ID NO:179) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2

SDF-1(1-17)-[linker]-MIP-1α (35-49)-acid or amide

f173) (SEQ ID NO:180) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH) NH2 f174) (SEQ ID NO:181) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f175) (SEQ ID NO:182) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f176) (SEQ ID NO:183) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f177) (SEQ ID NO:184) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f178) (SEQ ID NO:185) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f179) (SEQ ID NO:186) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f180) (SEQ ID NO:187) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f181) (SEQ ID NO:188) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f182) (SEQ ID NO:189) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f183) (SEQ ID NO:190) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f184) (SEQ ID NO:191) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f185) (SEQ ID NO:192) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f186) (SEQ ID NO:193) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f187) (SEQ ID NO:194) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f188) (SEQ ID NO:195) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f189) (SEQ ID NO:196) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f190) (SEQ ID NO:197) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f191) (SEQ ID NO:198) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f192) (SEQ ID NO:199) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f193) (SEQ ID NO:200) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa1-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f194) (SEQ ID NO:201) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f195) (SEQ ID NO:202) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f196) (SEQ ID NO:203) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f197) (SEQ ID NO:204) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f198) (SEQ ID NO:205) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f199) (SEQ ID NO:206) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f200) (SEQ ID NO:207) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH) NH2 f201) (SEQ ID NO:208) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f202) (SEQ ID NO:209) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f203) (SEQ ID NO:210) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f204) (SEQ ID NO:211) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f205) (SEQ ID NO:212) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f206) (SEQ ID NO:213) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f207) (SEQ ID NO:214) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f208) (SEQ ID NO:215) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f209) (SEQ ID NO:216) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f210) (SEQ ID NO:217) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f211) (SEQ ID NO:218) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f212) (SEQ ID NO:219) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f213) (SEQ ID NO:220) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f214) (SEQ ID NO:221) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f215) (SEQ ID NO:222) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f216) (SEQ ID NO:223) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f217) (SEQ ID NO:224) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f218) (SEQ ID NO:225) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH) NH2 f219) (SEQ ID NO:226) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f220) (SEQ ID NO:227) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f221) (SEQ ID NO:228) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f222) (SEQ ID NO:229) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f223) (SEQ ID NO:230) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f224) (SEQ ID NO:231) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f225) (SEQ ID NO:232) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f226) (SEQ ID NO:233) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f227) (SEQ ID NO:234) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH) NH2 f228) (SEQ ID NO:235) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f229) (SEQ ID NO:236) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f230) (SEQ ID NO:237) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f231) (SEQ ID NO:238) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f232) (SEQ ID NO:239) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f233) (SEQ ID NO:240) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f234) (SEQ ID NO:241) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f235) (SEQ ID NO:242) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2

SDF-1(1-17)-[linker]-MIP-1α (55-69)-acid or amide

f236) (SEQ ID NO:243) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH) NH2 f237) (SEQ ID NO:244) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f238) (SEQ ID NO:245) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f239) (SEQ ID NO:246) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f240) (SEQ ID NO:247) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f241) (SEQ ID NO:248) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f242) (SEQ ID NO:249) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f243) (SEQ ID NO:250) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f244) (SEQ ID NO:251) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f45) (SEQ ID NO:252) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f246) (SEQ ID NO:253) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f247) (SEQ ID NO:254) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f248) (SEQ ID NO:255) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f249) (SEQ ID NO:256) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f250) (SEQ ID NO:257) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f251) (SEQ ID NO:258) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f252) (SEQ ID NO:259) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f253) (SEQ ID NO:260) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f254) (SEQ ID NO:261) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f255) (SEQ ID NO:262) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f256) (SEQ ID NO:263) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f257) (SEQ ID NO:264) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f258) (SEQ ID NO:265) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f259) (SEQ ID NO:266) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f260) (SEQ ID NO:267) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f261) (SEQ ID NO:268) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f262) (SEQ ID NO:269) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f263) (SEQ ID NO:270) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f264) (SEQ ID NO:271) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f265) (SEQ ID NO:272) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f266) (SEQ ID NO:273) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f267) (SEQ ID NO:274) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f268) (SEQ ID NO:275) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f269) (SEQ ID NO:276) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f270) (SEQ ID NO:277) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f271) (SEQ ID NO:278) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f272) (SEQ ID NO:279) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f273) (SEQ ID NO:280) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f274) (SEQ ID NO:281) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f275) (SEQ ID NO:282) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f276) (SEQ ID NO:283) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f277) (SEQ ID NO:284) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f278) (SEQ ID NO:285) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f279) (SEQ ID NO:286) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f280) (SEQ ID NO:287) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f281) (SEQ ID NO:288) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f282) (SEQ ID NO:289) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f283) (SEQ ID NO:290) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f284) (SEQ ID NO:291) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f285) (SEQ ID NO:292) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f286) (SEQ ID NO:293) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f287) (SEQ ID NO:294) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f288) (SEQ ID NO:295) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f289) (SEQ ID NO:296) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f290) (SEQ ID NO:297) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f291) (SEQ ID NO:298) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f292) (SEQ ID NO:299) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f293) (SEQ ID NO:300) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f294) (SEQ ID NO:301) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f295) (SEQ ID NO:302) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f296) (SEQ ID NO:303) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f297) (SEQ ID NO:304) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f298) (SEQ ID NO:305) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2

Preferred embodiments of cyclic SDF-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 SDF-1 having the following structures:

SDF-1(1-14)-[linker]-SDF-1(55-67)-cyclic(Glu60-Lys64) acid or amide:

f299) (SEQ ID NO:306) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f300) (SEQ ID NO:307) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f301) (SEQ ID NO:308) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f302) (SEQ ID NO:309) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f303) (SEQ ID NO:310) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f304) (SEQ ID NO:311) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f305) (SEQ ID NO:312) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f306) (SEQ ID NO:313) RHN-Lys-Pro-Val-Ser-Leu- Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f307) (SEQ ID NO:314) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f309) (SEQ ID NO:315) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f310) (SEQ ID NO:316) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f311) (SEQ ID NO:317) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f312) (SEQ ID NO:318) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f313) (SEQ ID NO:319) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f314) (SEQ ID NO:320) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f315) (SEQ ID NO:321) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f316) (SEQ ID NO:322) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f317) (SEQ ID NO:323) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f318) (SEQ ID NO:324) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f319) (SEQ ID NO:325) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f320) (SEQ ID NO:326) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f321) (SEQ ID NO:327) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f322) (SEQ ID NO:328) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f323) (SEQ ID NO:329) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f324) (SEQ ID NO:330) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f325) (SEQ ID NO:331) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f326) (SEQ ID NO:332) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f327) (SEQ ID NO:333) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f328) (SEQ ID NO:334) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f329) (SEQ ID NO:335) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f330) (SEQ ID NO:336) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f331) (SEQ ID NO:337) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f332) (SEQ ID NO:338) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f334) (SEQ ID NO:339) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f335) (SEQ ID NO:340) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f336) (SEQ ID NO:341) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2

SDF-1(1-17)-[linker]-SDF-1(55-67)-cyclic(Glu60-Lys64) acid or amide:

f337) (SEQ ID NO:342) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f338) (SEQ ID NO:343) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f339) (SEQ ID NO:344) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f340) (SEQ ID NO:345) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f341) (SEQ ID NO:346) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f342) (SEQ ID NO:347) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f343) (SEQ ID NO:348) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f344) (SEQ ID NO:349) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f345) (SEQ ID NO:350) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaal-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f346) (SEQ ID NO:351) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f347) (SEQ ID NO:352) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f348) (SEQ ID NO:353) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f349) (SEQ ID NO:354) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f350) (SEQ ID NO:355) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f351) (SEQ ID NO:356) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f352) (SEQ ID NO:357) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f353) (SEQ ID NO:358) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f354) (SEQ ID NO:359) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f355) (SEQ ID NO:360) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f356) (SEQ ID NO:361) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f357) (SEQ ID NO:362) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f358) (SEQ ID NO:363) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f359) (SEQ ID NO:364) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f360) (SEQ ID NO:365) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f361) (SEQ ID NO:366) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f362) (SEQ ID NO:367) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f363) (SEQ ID NO:368) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f364) (SEQ ID NO:369) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f365) (SEQ ID NO:370) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f366) (SEQ ID NO:371) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f367) (SEQ ID NO:372) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f368) (SEQ ID NO:373) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f369) (SEQ ID NO:374) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f370) (SEQ ID NO:375) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f371) (SEQ ID NO:376) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f372) (SEQ ID NO:377) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f373) (SEQ ID NO:378) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f374) (SEQ ID NO:379) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f375) (SEQ ID NO:380) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa4-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f376) (SEQ ID NO:381) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f377) (SEQ ID NO:382) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f378) (SEQ ID NO:383) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Gh4-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f379) (SEQ ID NO:384) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f380) (SEQ ID NO:385) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f381) (SEQ ID NO:386) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f382) (SEQ ID NO:387) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f383) (SEQ ID NO:388) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f384) (SEQ ID NO:389) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f385) (SEQ ID NO:390) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f386) (SEQ ID NO:391) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f387) (SEQ ID NO:392) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f388) (SEQ ID NO:393) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f389) (SEQ ID NO:394) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f390) (SEQ ID NO:395) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f391) (SEQ ID NO:396) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f392) (SEQ ID NO:397) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f393) (SEQ ID NO:398) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f394) (SEQ ID NO:399) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f395) (SEQ ID NO:400) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f396) (SEQ ID NO:401) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f397) (SEQ ID NO:402) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f398) (SEQ ID NO:403) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f399) (SEQ ID NO:404) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2

SDF-1(1-14)-[linker]-SDF-1(55-67)-cyclic(Lys56-Glu60) acid or amide:

f400) (SEQ ID NO:405) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f401) (SEQ ID NO:406) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f402) (SEQ ID NO:407) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f403) (SEQ ID NO:408) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f404) (SEQ ID NO:409) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f405) (SEQ ID NO:410) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f406) (SEQ ID NO:411) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f407) (SEQ ID NO:412) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f408) (SEQ ID NO:413) RHN-Lys-Pro-Val-Ser-Leu- Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f409) (SEQ ID NO:414) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f410) (SEQ ID NO:415) RHN-Xaa3-Pro-Val-Ser-Leu- Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f411) (SEQ ID NO:416) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f412) (SEQ ID NO:417) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f413) (SEQ ID NO:418) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-GLu-Lys-Ala-Leu-Asn-(OH)NH2 f414) (SEQ ID NO:419) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f415) (SEQ ID NO:420) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f416) (SEQ ID NO:421) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f417) (SEQ ID NO:422) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f418) (SEQ ID NO:423) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f419) (SEQ ID NO:424) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f420) (SEQ ID NO:425) RHN-Lys-Xaa3-Va1-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f421) (SEQ ID NO:426) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f422) (SEQ ID NO:427) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f423) (SEQ ID NO:428) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f424) (SEQ ID NO:429) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f425) (SEQ ID NO:430) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f426) (SEQ ID NO:431) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f427) (SEQ ID NO:432) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f428) (SEQ ID NO:433) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f429) (SEQ ID NO:434) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f430) (SEQ ID NO:435) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f431a) (SEQ ID NO:436) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f432a) (SEQ ID NO:437) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f433a) (SEQ ID NO:438) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f431b) (SEQ ID NO:439) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f432b) (SEQ ID NO:440) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2

SDF-1(1-17)-[linker]-SDF-1(55-67)-cyclic(Lys56-Glu60) acid or amide:

f433b) (SEQ ID NO:441) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f434) (SEQ ID NO:442) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f435) (SEQ ID NO:443) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f436) (SEQ ID NO:444) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f437) (SEQ ID NO:445) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f438) (SEQ ID NO:446) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f439) (SEQ ID NO:447) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f440) (SEQ ID NO:448) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f441) (SEQ ID NO:449) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f442) (SEQ ID NO:450) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f443) (SEQ ID NO:451) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f444) (SEQ ID NO:452) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f445) (SEQ ID NO:453) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f446) (SEQ ID NO:454) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f447) (SEQ ID NO:455) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f448) (SEQ ID NO:456) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f449) (SEQ ID NO:457) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f450) (SEQ ID NO:458) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f451) (SEQ ID NO:459) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f452) (SEQ ID NO:460) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f453) (SEQ ID NO:461) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f454) (SEQ ID NO:462) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f455) (SEQ ID NO:463) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f456) (SEQ ID NO:464) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f457) (SEQ ID NO:465) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f458) (SEQ ID NO:466) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f459) (SEQ ID NO:467) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f460) (SEQ ID NO:468) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f461) (SEQ ID NO:469) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f462) (SEQ ID NO:470) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f463) (SEQ ID NO:471) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f464) (SEQ ID NO:472) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f465) (SEQ ID NO:473) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f466) (SEQ ID NO:474) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f467) (SEQ ID NO:475) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f468) (SEQ ID NO:476) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f469) (SEQ ID NO:477) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f470) (SEQ ID NO:478) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f471) (SEQ ID NO:479) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f472) (SEQ ID NO:480) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f473) (SEQ ID NO:481) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f474) (SEQ ID NO:482) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f475) (SEQ ID NO:483) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f476) (SEQ ID NO:484) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f477) (SEQ ID NO:485) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f478) (SEQ ID NO:486) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f479) (SEQ ID NO:487) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f480) (SEQ ID NO:488) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f481) (SEQ ID NO:489) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f482) (SEQ ID NO:490) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f483) (SEQ ID NO:491) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f484) (SEQ ID NO:492) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f485) (SEQ ID NO:493) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f486) (SEQ ID NO:494) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f487) (SEQ ID NO:495) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-(OH)NH2 f488) (SEQ ID NO:496) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f489) (SEQ ID NO:497) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f490) (SEQ ID NO:498) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f491) (SEQ ID NO:499) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f492) (SEQ ID NO:500) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f493) (SEQ ID NO:501) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f494) (SEQ ID NO:502) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2 f495) (SEQ ID NO:503) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Leu-Lys- Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn- (OH)NH2

Similarly, cyclic polypeptides may be prepared using sequences from chemokines other than SDF-1. Such as residues 35-49, 10-49, or 55-69 of MIP-1α:

For instance preferred embodiments of cyclic hybrid analogs: SDF-1/MIP-1α were prepared by linking together the SDF-1 N-terminal region and residues 35-49 of the MIP-1α C-terminal region. The C-terminal region was cyclized by etherification reaction between residue Thr44 and residue Ser47 (underlined).

SDF-1(1-14)-[linker]-MIP-1α (35-49)-cyclic(Thr44-Ser47) acid or amide

f496) (SEQ ID NO:504) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val-Ile-Phe- Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f497) (SEQ ID NO:505) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f498) (SEQ ID NO:506) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f499) (SEQ ID NO:507) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f500) (SEQ ID NO:508) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f501) (SEQ ID NO:509) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f502) (SEQ ID NO:510) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f503) (SEQ ID NO:511) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f504) (SEQ ID NO:512) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f505) (SEQ ID NO:513) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f506) (SEQ ID NO:514) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f507) (SEQ ID NO:515) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f508) (SEQ ID NO:516) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f509) (SEQ ID NO:517) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f510) (SEQ ID NO:518) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f511) (SEQ ID NO:519) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f512) (SEQ ID NO:520) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f513) (SEQ ID NO:521) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f514) (SEQ ID NO:522) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f515) (SEQ ID NO:523) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f516) (SEQ ID NO:524) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f517) (SEQ ID NO:525) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f518) (SEQ ID NO:526) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f519) (SEQ ID NO:527) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f520) (SEQ ID NO:528) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f521) (SEQ ID NO:529) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f522) (SEQ ID NO:530) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f523) (SEQ ID NO:531) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f524) (SEQ ID NO:532) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f525) (SEQ ID NO:533) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f526) (SEQ ID NO:534) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f527) (SEQ ID NO:535) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f528) (SEQ ID NO:536) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f529) (SEQ ID NO:537) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f530) (SEQ ID NO:538) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f531) (SEQ ID NO:539) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Ser-Lys-Pro-Gly-Val- Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val-(OH)NH2 f532) (SEQ ID NO:540) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2

SDF-1(1-17)-[linker]-MIP-1α (35-49)-cyclic(Thr44-Ser47) acid or amide

f533) (SEQ ID NO:541) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f534) (SEQ ID NO:542) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f535) (SEQ ID NO:543) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f536) (SEQ ID NO:544) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f537) (SEQ ID NO:545) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f538) (SEQ ID NO:546) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f539) (SEQ ID NO:547) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f540) (SEQ ID NO:548) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro- Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f541) (SEQ ID NO:549) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f542) (SEQ ID NO:550) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f543) (SEQ ID NO:551) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f544) (SEQ ID NO:552) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f545) (SEQ ID NO:553) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f546) (SEQ ID NO:554) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f547) (SEQ ID NO:555) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f548) (SEQ ID NO:556) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f549) (SEQ ID NO:557) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f550) (SEQ ID NO:558) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f551) (SEQ ID NO:559) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f552) (SEQ ID NO:560) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f553) (SEQ ID NO:561) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f554) (SEQ ID NO:562) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f555) (SEQ ID NO:563) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f556) (SEQ ID NO:564) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f557) (SEQ ID NO:565) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f558) (SEQ ID NO:566) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f559) (SEQ ID NO:567) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f560) (SEQ ID NO:568) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f561) (SEQ ID NO:569) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f562) (SEQ ID NO:570) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f563) (SEQ ID NO:571) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f564) (SEQ ID NO:572) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f565) (SEQ ID NO:573) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f566) (SEQ ID NO:574) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f567) (SEQ ID NO:575) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f568) (SEQ ID NO:576) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f569) (SEQ ID NO:577) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f570) (SEQ ID NO:578) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f571) (SEQ ID NO:579) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaas-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f572) (SEQ ID NO:580) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f573) (SEQ ID NO:581) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f574) (SEQ ID NO:582) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f575) (SEQ ID NO:583) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f576) (SEQ ID NO:584) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f577) (SEQ ID NO:585) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys-Pro-Gly- Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- (OH)NH2 f578) (SEQ ID NO:586) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f579) (SEQ ID NO:587) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f580) (SEQ ID NO:588) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f581) (SEQ ID NO:589) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f582) (SEQ ID NO:590) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f583) (SEQ ID NO:591) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f584) (SEQ ID NO:592) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f585) (SEQ ID NO:593) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f586) (SEQ ID NO:594) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f587) (SEQ ID NO:595) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f588) (SEQ ID NO:596) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f589) (SEQ ID NO:597) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f590) (SEQ ID NO:598) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f591) (SEQ ID NO:599) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f592) (SEQ ID NO:600) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f593) (SEQ ID NO:601) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2 f594) (SEQ ID NO:602) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Ser-Lys- Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln- Val-(OH)NH2

More preferred embodiments of cyclic hybrid analogs: SDF-1/MIP-1α were prepared by linking together the SDF-1 N-terminal region and residues 56-69 of the MIP-1α C-terminal region. The C-terminal region was cyclized by lactamization reaction between residue Lys61 and residue Asp64 (underlined).

SDF-(1-14)-[linker]-MIP-1α (55-69)-cyclic(Lys61-Asp64) acid or amide

f595) (SEQ ID NO:603) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f596) (SEQ ID NO:604) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f597) (SEQ ID NO:605) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f598) (SEQ ID NO:606) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f599) (SEQ ID NO:607) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f600) (SEQ ID NO:608) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ma-(OH)NH2 f601) (SEQ ID NO:609) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f602) (SEQ ID NO:610) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f603) (SEQ ID NO:611) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f604) (SEQ ID NO:612) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f605) (SEQ ID NO:613) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f606) (SEQ ID NO:614) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f607) (SEQ ID NO:615) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f608) (SEQ ID NO:616) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f609) (SEQ ID NO:617) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f610) (SEQ ID NO:618) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f611) (SEQ ID NO:619) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f612) (SEQ ID NO:620) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f613) (SEQ ID NO:621) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f614) (SEQ ID NO:622 RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f615) (SEQ ID NO:623) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f616) (SEQ ID NO:624) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f617) (SEQ ID NO:625) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f618) (SEQ ID NO:626) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f619) (SEQ ID NO:627) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f620) (SEQ ID NO:628) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f621) (SEQ ID NO:629) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f622) (SEQ ID NO:630) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f623) (SEQ ID NO:631) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f624) (SEQ ID NO:632) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f625) (SEQ ID NO:633) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f626) (SEQ ID NO:634) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f627) (SEQ ID NO:635) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f628) (SEQ ID NO:636) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f629) (SEQ ID NO:637) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f630) (SEQ ID NO:638) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2

SDF-1(1-17)-[linker]-MIP-1α (55-69)-cyclic(Lys61-Asp64) acid or amide

f631) (SEQ ID NO:639) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f632) (SEQ ID NO:640) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f633) (SEQ ID NO:641) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f634) (SEQ ID NO:642) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f635) (SEQ ID NO:643) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f636) (SEQ ID NO:644) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f637) (SEQ ID NO:645) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f638) (SEQ ID NO:646) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f639) (SEQ ID NO:647) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp- Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f640) (SEQ ID NO:648) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH) NH2 f641) (SEQ ID NO:649) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f642) (SEQ ID NO:650) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f643) (SEQ ID NO:651) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f644) (SEQ ID NO:652) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f645) (SEQ ID NO:653) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f646) (SEQ ID NO:654) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f647) (SEQ ID NO:655) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f648) (SEQ ID NO:656) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f649) (SEQ ID NO:657) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f650) (SEQ ID NO:658) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f651) (SEQ ID NO:659) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f652) (SEQ ID NO:660) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f653) (SEQ ID NO:661) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f654) (SEQ ID NO:662) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f655) (SEQ ID NO:663) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f656) (SEQ ID NO:664) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f657) (SEQ ID NO:665) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f658) (SEQ ID NO:666) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH) NH2 f659) (SEQ ID NO:667) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f660) (SEQ ID NO:668) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f661) (SEQ ID NO:669) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f662) (SEQ ID NO:670) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f663) (SEQ ID NO:671) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f664) (SEQ ID NO:672) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f665) (SEQ ID NO:673) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f666) (SEQ ID NO:674) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f667) (SEQ ID NO:675) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH) NH2 f668) (SEQ ID NO:676) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f669) (SEQ ID NO:677) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f670) (SEQ ID NO:678) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-GIn-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f671) (SEQ ID NO:679) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f672) (SEQ ID NO:680) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f673) (SEQ ID NO:681) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f674) (SEQ ID NO:682) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f675) (SEQ ID NO:683) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f676) (SEQ ID NO:684) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f677) (SEQ ID NO:685) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f678) (SEQ ID NO:686) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f679) (SEQ ID NO:687) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f680) (SEQ ID NO:688) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f681) (SEQ ID NO:689) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f682) (SEQ ID NO:690) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f683) (SEQ ID NO:691) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f684) (SEQ ID NO:692) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f685) (SEQ ID NO:693) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f686) (SEQ ID NO:694) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f687) (SEQ ID NO:695) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f688) (SEQ ID NO:696) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f689) (SEQ ID NO:697) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f690) (SEQ ID NO:698) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f691) (SEQ ID NO:699) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f692) (SEQ ID NO:700) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f693) (SEQ ID NO:701) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2

SDF-(1-14)-[linker]-MIP-1α (55-69)-cyclic(Glu57-Lys61) acid or amide

f694) (SEQ ID NO:702) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f695) (SEQ ID NO:703) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f696) (SEQ ID NO:704) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f697) (SEQ ID NO:705) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f698) (SEQ ID NO:706) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f699) (SEQ ID NO:707) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f700) (SEQ ID NO:708) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f701) (SEQ ID NO:709) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f702) (SEQ ID NO:710) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys- Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f703) (SEQ ID NO:711) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f705) (SEQ ID NO:712) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f706) (SEQ ID NO:713) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f707) (SEQ ID NO:714) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f708) (SEQ ID NO:715) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f709) (SEQ ID NO:716) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f710) (SEQ ID NO:717) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f712) (SEQ ID NO:718) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f713) (SEQ ID NO:719) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f714) (SEQ ID NO:720) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln-Lys-Tyr- Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f715) (SEQ ID NO:721) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f716) (SEQ ID NO:722) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f717) (SEQ ID NO:723) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f718) (SEQ ID NO:724) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f719) (SEQ ID NO:725) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f720) (SEQ ID NO:726) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f721) (SEQ ID NO:727) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f722) (SEQ ID NO:728) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f723) (SEQ ID NO:729) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f724) (SEQ ID NO:730) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f725) (SEQ ID NO:731) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f726) (SEQ ID NO:732) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f727) (SEQ ID NO:733) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f728) (SEQ ID NO:734) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f729) (SEQ ID NO:735) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f730) (SEQ ID NO:736) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2 f731) (SEQ ID NO:737) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-[linker]-Glu-Glu-Trp-Val-Gln- Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH2

SDF-1(1-17)-[linker]-MIP-1α (55-69)-cyclic(Glu57-Lys61) acid or amide

f732) (SEQ ID NO:738) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f733) (SEQ ID NO:739) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu- Ser-Ala-(OH)NH2 f734) (SEQ ID NO:740) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f735) (SEQ ID NO:741) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f736) (SEQ ID NO:742) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f737) (SEQ ID NO:743) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f738) (SEQ ID NO:744) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f739) (SEQ ID NO:745) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f740) (SEQ ID NO:746) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f741) (SEQ ID NO:747) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Gln- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f742) (SEQ ID NO:748) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f743) (SEQ ID NO:749) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f744) (SEQ ID NO:750) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f745) (SEQ ID NO:751) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f746) (SEQ ID NO:752) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f747) (SEQ ID NO:753) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f748) (SEQ ID NO:754) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f749) (SEQ ID NO:755) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Xaa4-Phe-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f750) (SEQ ID NO:756) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f751) (SEQ ID NO:757) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f752) (SEQ ID NO:758) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f753) (SEQ ID NO:759) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f754) (SEQ ID NO:760) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Lys- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f755) (SEQ ID NO:761) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f756) (SEQ ID NO:762) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f757) (SEQ ID NO:763) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f758) (SEQ ID NO:764) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Xaa4-Phe-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f759) (SEQ ID NO:765) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f760) (SEQ ID NO:766) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f761) (SEQ ID NO:767) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f762) (SEQ ID NO:768) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f763) (SEQ ID NO:769) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f764) (SEQ ID NO:770) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f765) (SEQ ID NO:771) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f766) (SEQ ID NO:772) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f767) (SEQ ID NO:773) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Xaa4-Glu-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f768) (SEQ ID NO:774) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f769) (SEQ ID NO:775) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f770) (SEQ ID NO:776) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f771) (SEQ ID NO:777) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f772) (SEQ ID NO:778) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f773) (SEQ ID NO:779) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f774) (SEQ ID NO:780) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f775) (SEQ ID NO:781) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f776) (SEQ ID NO:782) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Xaa4-Ser-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f777) (SEQ ID NO:783) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu-Trp-Val- Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala- (OH)NH2 f778) (SEQ ID NO:784) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f779) (SEQ ID NO:785) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f780) (SEQ ID NO:786) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f781) (SEQ ID NO:787) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f782) (SEQ ID NO:788) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f783) (SEQ ID NO:789) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f784) (SEQ ID NO:790) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f785) (SEQ ID NO:791) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Xaa4-His-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f786) (SEQ ID NO:792) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f787) (SEQ ID NO:793) RHN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f788) (SEQ ID NO:794) RHN-Lys-Xaa3-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f789) (SEQ ID NO:795) RHN-Lys-Pro-Xaa3-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f790) (SEQ ID NO:796) RHN-Lys-Pro-Val-Xaa3-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f791) (SEQ ID NO:797) RHN-Lys-Pro-Val-Ser-Xaa3-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f792) (SEQ ID NO:798) RHN-Lys-Pro-Val-Ser-Leu-Xaa3-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f793) (SEQ ID NO:799) RHN-Lys-Pro-Val-Ser-Leu-Ser-Xaa3-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa4-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2 f794) (SEQ ID NO:800) RHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Xaa3-Xaa1-Pro- Xaa2-Arg-Phe-Phe-Glu-Ser-Xaa1-[linker]-Glu-Glu- Trp-Val-Gln-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser- Ala-(OH)NH2

In the above sequences:

R is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol) and any other modifying group.

Xaa3 is selected from the group consisting of L-Pro, D-Pro, P*, Btd and any L- or D-natural and non-natural amino acid.

Xaa4 is 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
Z may be hydrogen, alkyl alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, or aryl-hydroxy.

A wide variety of amino acid substitutions may be made in polypeptide sequences, such as lysine to glutamic acid, lysine to aspartic acid, glutamic acid (Glu) to ornithine (Orn), aspartic acid (Asp) to ornithine (Orn). Moieties other than naturally occurring amino acids may also be substituted, such as Btd:
Btd* is:
Z may be hydrogen, alkyl alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, aryl, or aryl-hydroxy.
Xaa1 is selected from the group consisting of any L- or D-natural amino acid and any non-natural amino acid.
Xaa2 is 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-ZA-COOH wherein ZA is 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 4 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, prophylactically, or diagnostically 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, or assist in vaccine production.

An “effective amount” of a compound of the invention includes a therapeutically effective amount or a prophylactically 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 subjects 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 of lymphocytic cells to respond 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; (i) inhibiting an enzyme activity present in cells associated with the abnormal condition; and (j) decreasing or arresting the progression of a cell through the cell cycle.

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.

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, polyanhydrides, 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 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. Signal transduction complexes often contain 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 mixing a solution 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. 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 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

This example illustrates the efficacy of SDF-1 and SDF-1 peptide analogs in mediating intracellular calcium mobilization ([Ca2+]i). To illustrate that the binding of SDF-1 and SDF-1 peptide analogs results in the agonistic activation of the CXCR4 receptor, [Ca2+]i mobilization assays were conducted, the results of which are shown in FIG. 1. Fluo-4,AM loaded SUP-T1 cells (5×106 cells/ml), a human lymphoid cell line, were stimulated with SDF-1 and Compound A (SEQ ID NO:809), Compound B (SEQ ID NO:810), Compound C (SEQ ID NO:811), Compound D (SEQ ID NO:812) and Compound E (SEQ ID NO:813) at the concentrations indicated. The values represent the mean+/−one S.D. of a representative experiment from three independent experiments. As shown by the data in FIG. 1, incubation of SUP-T1 cells with SDF-1 or Compound A (SEQ ID NO:809), Compound B (SEQ ID NO:810), Compound C (SEQ ID NO:811), Compound D (SEQ ID NO:812) or Compound E (SEQ ID NO:813) resulted in the receptor-mediated induction of [Ca2+]i mobilization. (The underlined residues in the structures depicted below were cyclized by a lactamization reaction between lysine and glutamic acid residues.)

Compound A or f400 (SEQ ID NO:405), wherein R═H, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly)

(SEQ ID NO:809) H2N-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound B or f400 (SEQ ID NO:405), wherein R═H, Xaa1=Ala, Xaa2=Phe, [linker]=4×Gly)

(SEQ ID NO:810) H2N-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Ala-Pro-Phe- Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound C or f400 (SEQ ID NO:405), wherein R═Ac, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly)

(SEQ ID NO:811) AcHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound D or f400 (SEQ ID NO:405), wherein R═Ac, Xaa1=Cys, Xaa2=Cys, [linker]=1 aminoundecanoic acid)

(SEQ ID NO:812) AcHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[11 aminoundecanoic acid]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound E or f401 (SEQ ID NO:406), wherein Xaa3=desLys, Xaa=Cys, Xaa2=Cys, [linker]=4×Gly)

(SEQ ID NO:813) H2N-[desNH2Lys]-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys- Pro-Cys-Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound F or f402 (SEQ ID NO:407), wherein Xaa3=D-Pro, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly)

(SEQ ID NO:814) H2N-Lys-[D-Pro]-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro- Cys-Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound G or f405 (SEQ ID NO:410), wherein Xaa3=D-Leu, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly)

(SEQ ID NO:815) H2N-Lys-Pro-Val-Ser-[D-Leu]-Ser-Tyr-Arg-Cys-Pro- Cys-Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound H or f400 (SEQ ID NO:405), wherein R═H, Xaa1=Cys, Xaa2=Cys, [linker]=11aminoundecanoic acid

(SEQ ID NO:816) H2N-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[11 aminoundecanoic acid]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

The [Ca2+]i mobilization assays were conducted as follows. Briefly, SUP-T1 cells (ATCC, Manassas, Va.), a human lymphoid cell line, were cultured in RPMI containing phenol red (Invitrogen, Burlington, Ontario, Canada) with 10% fetal bovine serum and antibiotics consisting of 100 U/ml penicillin G sodium and 100 μg/ml streptomycin sulfate (Invitrogen) at a density between 2×105 and 8×105 cells/ml. Cells were harvested and suspended in Tyrode's salt solution, consisting of 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mM CaCl2, 0.2 mM NaH2PO4, 12 mM NaHCO3, and 5.5 mM glucose, at 2×106 cells/ml then labeled with 4 μM Fluo-4/AM (Molecular Probes, Eugene, Oreg.) for 45 min at 37° C. Subsequently, cells were washed three times with Tyrode's salt solution, and resuspended at 5×106 cells/ml. SDF-1, Compound A (SEQ ID NO:809), Compound B (SEQ ID NO:810), Compound C (SEQ ID NO:811), Compound D (SEQ ID NO:812) or Compound E (SEQ ID NO:813) at the concentrations indicated were injected into aliquots of 5×105 cells. Changes in the level of cellular fluorescence were read in a Thermo Labsystems Fluorskan Acsent fluorescence plate reader (VWR, Mississauga, Ontario, Canada). Controls include cells treated with the recombinant chemokine or plain medium. Data is expressed with 100% being the level of fluorescence in plain medium. The values represent the mean+/−one S.D. of a representative experiment from three independent experiments. As shown by the data in FIG. 1, incubation of SUP-T1 cells with SDF-1, Compound A (SEQ ID NO:809), Compound B (SEQ ID NO:810), Compound C (SEQ ID NO:811), Compound D (SEQ ID NO:812) or Compound E (SEQ ID NO:813) resulted in the receptor-mediated induction of [Ca2+]i mobilization.

Example 2

The efficacy of SDF-1 and SDF-1 peptide analogs as CXCR4 agonists was demonstrated through CXCR4 receptor binding assays. A competitive dose response for binding to the SDF-1 receptor by native SDF-1 and the CXCR4 agonists (competing ligands) against 125I-SDF-1 is shown in FIG. 2. Briefly, SUP-T1 cells were grown as in Example 1. Millipore MultiScreen plates with Durapore membrane (Millipore, Bedford, Mass.) were used for high throughput binding assays. The buffer used for the assay (binding buffer) consisted of 0.1% bovine albumin, 25 mM HEPES, 100 μg/ml chondroitin sulphate C, and 0.02% sodium azide in RPMI-1640. SUP-T1 cells were harvested, washed with plain RPMI and resuspended in binding buffer at 5×106 cells/ml. The Durapore membrane of the Millipore MultiScreen plates was moistened with blocking buffer containing 0.5% BSA (Sigma), 50 mM HEPES, 150 mM NaCl, 5 mM MgCl2, 1 mM CaCl2 and 0.02% sodium azide for 40 min before use. To the wells were added binding buffer, antagonist, the appropriate radiolabeled chemokine, and the appropriate cells. Cells were preincubated with peptide analogs for 30 min then incubated with 125I-SDF-1 for 2 h with shaking at 4° C. SDF-1 peptide analogs were used at concentrations indicated along with 0.5 nM radiolabeled SDF-1. After three washes with cold PBS, plates were dried and radioactivity counted using a CliniGamma gamma counter (LKB Wallac, Gaithersburg, Md.). Controls include wells with only binding buffer and radiolabeled chemokine for background, and wells with binding buffer, unlabelled chemokine standard, radiolabeled chemokine and cells for standardization. The results are expressed as percentages of the maximal specific binding that was determined without competing ligand, and are the representative results from three independent experiments. A concentration-dependent inhibition of 125I-SDF-1 is illustrated, indicating the affinity of SDF-1 and SDF-1 peptide analogs for the receptor. The inhibition of 125I-SDF-1 binding by SDF-1 and the SDF-1 analogs is indicative of CXCR4 receptor binding.

Example 3

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% ethanol) 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, catalog No: T-9284).

Activating Agents: 2-(H-benzotriazol-1yl) 1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU: M.W.=321.09. from Quantum Richelieu, 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 such as cysteine, 2,4,6-Collidine, 99% (M.W.=121.18,d=0.917, from Aldrich, catalog No: 14,238-7) is used: 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 were protected with: Boc; tBu; Trt groups: with 4 fold excess (from Peptides International, Bachem, Novabiochem, Chem-Impex Inc). Glu24 and Lys20 of the compound represented by SEQ ID NO:809 were 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 temperature or at 45° C. automatically with 4-fold excess in each coupling. The synthesis is interrupted after residue Leu19, numbering consecutively in the compound represented by SEQ ID NO:809. 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.=1 155.58×0.1 mmol peptide×3 fold=347 mg dissolved in 5% Acetic Acid; 2.5% NMM in CHCl3 to 0.14 M, under argon. The solution is added to the support-bound peptide previously removed from the column in a reactvial containing a small magnetic 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; then DCM/DMF (1:1), and finally DMF. A positive Kaiser test indicated the deprotection of the amino side chain 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 cyclization 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 (MilliQ) 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 the 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 (solvent 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 20 μl is applied onto the column. The main peak or the major peaks are collected, SpeedVac dried and molecular weight determined by mass spectrometry.

The structures of the compounds used in this study are shown below (underlined residues are cyclized).

Compound A or f400 (SEQ ID NO:405), wherein R═H, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly):

(SEQ ID NO:809) H2N-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound B or f400 (SEQ ID NO:405), wherein R═H, Xaa1=Ala, Xaa2=Phe, [linker]=4×Gly):

(SEQ ID NO:810) H2N-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Ala-Pro-Phe- Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound C or f400 (SEQ ID NO:405), wherein R═Ac, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly):

(SEQ ID NO:811) AcHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile-Gln- Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound D or f400 (SEQ ID NO:405), wherein R═Ac, Xaa1=Cys, Xaa2=Cys, [linker]=11 aminoundecanoic acid):

(SEQ ID NO:812) AcHN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[11 aminoundecanoic acid]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound E or f401 (SEQ ID NO:406), wherein Xaa3=desLys, Xaa—Cys, Xaa2=Cys, [linker]=4×Gly):

(SEQ ID NO:813) H2N-[desNH2Lys]-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys- Pro-Cys-Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound F or f402 (SEQ ID NO:407), wherein Xaa3=D-Pro, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly):

(SEQ ID NO:814) H2N-Lys-[D-Pro]-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro- Cys-Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound G or f405 (SEQ ID NO:410), wherein Xaa3=D-Pro, Xaa1=Cys, Xaa2=Cys, [linker]=4×Gly):

(SEQ ID NO:815) H2N-Lys-Pro-Val-Ser-[D-Pro]-Ser-Tyr-Arg-Cys-Pro- Cys-Arg-Phe-Phe-[Gly-Gly-Gly-Gly]-Leu-Lys-Trp-Ile- Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Compound H or f400 (SEQ ID NO:405), wherein R═H, Xaa1=Cys, Xaa2=Cys, [linker]=11aminoundecanoic acid:

(SEQ ID NO:816) H2N-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys- Arg-Phe-Phe-[11 aminoundecanoic acid]-Leu-Lys-Trp- Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

Example 4

This example illustrates the efficacy of SDF-1 peptide analogs (as represented by Compound A (SEQ ID NO:809) and Compound B (SEQ ID NO:810)) in mobilizing circulating neutrophils in a mouse model. Increases in the number of circulating neutrophils due to SDF-1 peptide analog administration is shown in Table 2. This study consisted of three groups of female Balb/c mice (Charles River, Wilmington, Mass.): an untreated control group of 6 mice and two 18-mouse test groups. Before the start of the study, 20-23 g mice were randomly grouped in appropriately labeled cages and identified by cage markings and shaved marks on the dorsal region. The two test groups were treated one time intravenously with SDF-1 analogs at a dose of 2.5 mg/kg in volumes approximating 200 μl. The evaluated end points included moribundity and complete blood counts with differentials. Blood samples were obtained from 6 mice from each test group at t=30 minutes, 1 hour and 24 hours post analog administration. Prior to blood collection, mice were weighed and anesthetized. Blood was collected via a 1 cc syringe and 25G needle (Becton Dickinson/VWR) by cardiac puncture. One fresh blood smear was produced. The remaining blood was expelled into a Becton Dickinson EDTA microtainer and mixed gently by 5 inversions. The smear and microtainer tubes were used for differential and CBC analysis on a CellDyn 3500 (Abbott Diagnostic Products, Mississauga, Ontario, Canada) and by veterinarians (Central Laboratory for Veterinarians, Langley, B.C, Canada). The differentials were used to evaluate the mobilization of neutrophils and were compared to the untreated control group. The results are expressed as percentage of the count from untreated control animals and are representative of at least two experiments each with six animals per treatment. A time-dependent mobilization of neutrophils to the circulation is shown, indicating the rapid and potent activity of the peptide analogs. Compound B (represented by SEQ ID NO:810) exhibits an especially rapid and sustained action.

TABLE 2 Percentage change in circulating neutrophils in Balb/c mice treated with 2.5 mg/kg of the designated compound compared to untreated control animals. Duration of treatment (hours) Compound ½ 1 24 Compound A 175% 299%  25% Compound B 348% 304% 113%

Example 5

This example illustrates the stability of SDF-1 chemokine analogs (as represented by Compound A (SEQ ID NO:809) and Compound B (SEQ ID NO:810)) in human plasma.

Methods

In Vitro Incubations of Chemokine Analogs with Plasma

Fresh blood was collected into heparinized tubes and spun down at room temperature for 15 minutes at 1500 g, and the plasma was removed and placed in another tube. The plasma was then cooled to 4° C. by incubation on ice, and centrifuged for 15 minutes at 1500 g at 4° C. The plasma was recovered and used immediately and the leftover was frozen at −20° C.

Fractions of 0.5 ml of human plasma were aliquoted in eppendorf tubes and incubated in a heated bath at 37° C. A quantity of 200 μg of Compound B (SEQ ID NO:810) or Compound A (SEQ ID NO:809) in water (10 μg/μL in water) was added subsequently to each fraction and incubated for T=0, 5, 10, 20, 30, 60, 120, 240, 360 and 420 minutes. At the end of the incubation, the fractions were quenched by the addition of 0.20 ml 1M trifluoroacetic acid (TFA) and the tubes agitated gently and kept on ice for 10 minutes. The tubes were then diluted further with 200 μL of a 0.05% solution of TFA.

The samples were then centrifuged at 5000 rpm for 45 min at 4° C. The supernatants were extracted on solid phase.

Solid Phase Extraction of Human Plasma Samples

Sep-pak C18 cartridges (VWR #BJ9000, 100 mg, 1 ml, octadecyl column C18)) were preconditioned with 80% acetonitrile/0.1% TFA (5×1 ml) followed by TFA 0.05% (5×1 ml). The quenched (acidified) plasma samples were aspirated and applied to the column, and washed with 2×1 ml of TFA 0.05% (eluate discarded) followed by extraction with 5×1 ml of (80% acetonitrile/0.1% TFA). The samples were then frozen and lyophilized.

Dry residue was resuspended in 200 μL of (20% acetonitrile/0.1% TFA) and spun down in a centrifuge to clarify the sample by centrifugation at 5000 rpm for 15 minutes at 22° C. before loading 50 μL on HPLC.

High Performance Liquid Chromatography

HPLC analysis was performed on the Gilson using the following column, mobile phase, and detection systems.

Column: Vydac C18 (5 μm, 250 mm × 4.6 mm) Injection volume: 50 μL Mobile phase: A: 0.1% TFA in water B: 0.1% TFA in acetonitrile Gradient: was 30-90% B in 45 min; Flow rate 1 ml/min Detection 214 nm

TABLE 3 Stability study of designated compound in human plasma. Percentage of compound remaining in plasma after incubation. Duration of incubation with plasma (minutes) Compound 0 5 10 20 30 60 120 240 360 420 Compound A 100% 32% 26% 21%  8%  9% ND ND ND ND Compound B 100% 67% 56% 67% 56% 77% 52% 43% 26% 17%
ND: not determined.

Example 6

Tables 4 and 5 show the effect of CXCR4 agonists on bone marrow progenitor cells, particularly primitive erythroid cells and primitive granulocytes, compared to mature granulocytes. To obtain the data in Tables 4 and 5, cells were pre-incubated with each of the compounds or saline alone (‘no drug’ as control). The cells were then exposed to high dose 3H-thymidine, a cytotoxic agent. Rapidly dividing cells accumulate proportionally more of the cytotoxic radioactive thymidine and as a result are preferentially killed. The relative proportion of cells killed by the thymidine treatment compared to the control is indicative of the relative effectiveness of the compounds in reducing cellular multiplication, i.e., decreasing the rate of cell cycle progression. A higher (or unchanged) proportion of killed cells compared to the control is indicative that a compound does not reduce cellular multiplication of the given cell type.

TABLE 4 Effect of CXCR4 Agonists on Bone Marrow Progenitor Cells Exposed to 3H-Thymidine. % CELL KILLED No drug (control) SDF-1 SDF-1(1-9)2 Primitive 71 2 9 Erythroid Primitive 46 1 1 Granulocyte Mature 39 45 42 Granulocyte

In Table 4, SDF-1 polypeptide (Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys-Pro-Cys-Arg-Phe-Phe-Glu-Ser-His-Val-Ala-Arg-Ala-Asn-Val-Lys-His-Leu-Lys-Ile-Leu-Asn-Thr-Pro-Asn-Cys-Ala-Leu-Gln-Ile-Val-Ala-Arg-Leu-Lys-Asn-Asn-Asn-Arg-Gln-Val-Cys-Ile-Asp-Pro-Lys-Leu-Lys-Trp-Ile-Gln-Glu-Tyr-Leu-Glu-Lys-Ala-Leu-Asn)(KPVSL SYRCP CRFFE SHVAR ANVKH LKILN TPNCA LQIVA RLKNN NRQVC IDPKL KWIQE YLEKA LN (SEQ ID NO: 1)) was used at 100 ng/ml on a human bone marrow cell culture. SDF-1(1-9)2 Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Cys -linker-(carboxy terminus)Cys-Arg-Tyr-Ser-Leu-Ser-Val-Pro-Lys(amino terminus) (SEQ ID NO:802)) was used at 50 μg/ml on a human bone marrow cell culture.

Table 5 further demonstrates that SDF-1(1-14)-(Gly)4-SDF-1(55-67)-amide (SEQ ID NO: 801) and SDF-1(1-14)-(Gly)4-SDF-1 (55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO: 809) were both able to inhibit cell cycling in human positive erythroid and primitive granulopoietic cells, but not in mature granulopoietic cells, in the assay as described above in this Example.

TABLE 5 % CELL KILLED No drug (control) Compound A Compound B Primitive 47 +/− 4 5 +/− 3  −7 +/− 6 Erythroid Primitive 42 +/− 3 1 +/− 6 −11 +/− 7 Granulocyte Mature 48 +/− 3 39 +/− 5    44 +/− 6 Granulocyte
    • Where: Compound I is SDF-1(1-14)-(Gly)4-SDF-1(55-67)-amide (SEQ ID NO:801);
      • Compound A is SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809)

Example 7

The present example demonstrates the therapeutic effectiveness of CXCR4 agonists in an animal model, showing protection of hematopoietic cells from cytotoxic treatments with CXCR4 agonists. In these animal studies, normal mice were treated with the cytotoxic chemotherapeutic agent arabinose-cytosine (Ara-C), which are known to deleteriously affect cells with high rates of DNA synthesis (reflecting rapid cell cycling).

As shown in the graph of FIG. 3, in mice given a single dose of Arabinose Cytosine (Ara-C) at 350 mg/kg at day zero intravenously, white blood cell count (WBC) decreases (due to the cytotoxic action of Ara-C). In contrast, in mice given the peptide SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809) (designated CTC in the graph legend) in combination with Ara-C, the extent of white blood cell count decrease is significantly ameliorated. In the graph, circular data points correspond to the white blood cell count in animals that received Ara-C but did not receive the peptide, and triangular data points are for animals that received Ara-C and SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809). The data clearly demonstrated the protective action of the peptide of the invention against the cytotoxic action of Ara-C.

Example 8

The efficacy of SDF-1 and SDF-1 peptide analogs as CXCR4 agonists was demonstrated through CXCR4 receptor binding assays. A competitive dose response for binding to the SDF-1 receptor by native SDF-1 (SEQ ID NO:1) and the CXCR4 agonists against 125I-SDF-1 is shown in FIGS. 4A and 4B respectively. A concentration-dependent inhibition of 125I-SDF-1 is illustrated in FIG. 4A, indicating the affinity of SDF-1 for the receptor. A Scatchard plot is illustrated, and the KD was determined to be 26 nM. SDF-1 and the indicated analogs (competing ligands) were added at the concentrations illustrated in the presence of 4 nM 125I-SDF-1. CEM cells were assessed for 125I-SDF-1 binding following 2 hr of incubation. The results are expressed as percentages of the maximal specific binding that was determined without competing ligand, and are the mean of three independent experiments. The inhibition of 125I-SDF-1 by SDF-1 and the SDF-1 analogs is indicative of CXCR4 receptor binding. The compounds illustrated in the figure are as follows: Compound A/SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809), Compound K/SDF-1(1-14)-(Gly)4-SDF-1(55-67)-Glu24/Lys28-cyclic amide (SEQ ID NO:803), Compound J/SDF-1 (1-9)2-Cys9/Cys9-cysteine dimer (SEQ ID NO:802), Compound N/SDF-1(1-17) (SEQ ID NO:804), Compound M/SDF-1 (1-8)2-lysine bridge dimer (SEQ ID NO:805) and Compound I/SDF-1(1-14)-(G)4-SDF-1(55-67) amide (SEQ ID NO:801).

Example 9

This example illustrates the efficacy of SDF-1 and SDF-1 peptide analogs in mediating intracellular calcium mobilization ([Ca2+]i). To illustrate that the binding of SDF-1 and SDF-1 peptide analogs results in the agonistic induction of the CXCR4 receptor, [Ca2+]i mobilization assays were conducted, the results of which are shown in FIG. 5. To obtain the data shown in FIG. 5, fura-2,AM loaded THP-1 cells (1×106/ml) were stimulated with Compound A/SDF-1, SDF-1(1-14)-(G)4-SDF-1(55-67) Lys20/Glu24-cyclic amide (SEQ ID NO:809) or Compound K/SDF-1(1-14)-(G)4-SDF-1(55-67)-Glu24/Lys28-cyclic amide (SEQ ID NO:803) at the concentrations indicated (the values represent the mean+/−one S.D. of n=3 experiments). As shown by the data in FIG. 5, incubation of THP-1 cells with SDF-1, SDF-1(1-14)-(G)4-SDF-1(55-67) Lys20/Glu24-cyclic amide (SEQ ID NO:809) or SDF-1(1-14)-(G)4-SDF-1(55-67)-Glu24/Lys28-cyclic amide (SEQ ID NO:803) resulted in the receptor-mediated induction of [Ca2+]i mobilization. The EC50 values (the concentration of ligand necessary to effectively induce 50% of the full [Ca2+]i mobilization potential) for SDF-1(1-14)-(G)4-SDF-1(55-67) acid (SEQ ID NO:806), SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809) or SDF-1(1-14)-(G)4-SDF-1(55-67)-Glu24/Lys28-cyclic amide (SEQ ID NO:803) and native SDF-1 is shown in Table 6:

TABLE 6 Compound EC50 (nM) SDF-1 26.56 SDF-1(1-14)-(Gly)4-SDF-1(55-67)- 106.25 Glu24/Lys28-cyclic amide (SEQ ID SDF-1(1-14)-(Gly)4-SDF-1(55-67)- 147.94 Lys20/Glu24-cyclic amide (SEQ ID SDF-1(1-14)-(Gly)4-SDF-1(55-67) acid 188.30 (SEQ ID NO: 806)

The comparative ability of SDF-1, Compound A/SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809), Compound K/SDF-1(1-14)-(G)4-SDF-1(55-67)-Glu24/Lys28-cyclic amide (SEQ ID NO:803), Compound J/SDF-1 (1-9)2-Cys9/Cys9-cysteine dimer (SEQ ID NO:802), Compound N/SDF-1(1-17) (SEQ ID NO:804), Compound M/SDF-1 (1-8)2-lysine bridge dimer (SEQ ID NO:805) and Compound I/SDF-1(1-14)-(G)4-SDF-1(55-67) amide (SEQ ID NO:801) to induce [Ca2+]i mobilization at the ligand concentration that the native SDF-1 gave maximal [Ca2+]i mobilization (1 μM, refer to FIG. 5) is illustrated in FIG. 6. Fura-2,AM loaded THP-1 cells (1×106/ml) were stimulated with native SDF-1 and the SDF-1 peptide agonist analogs at the concentration of native SDF-1 that gave the maximum [Ca2+]i stimulation (1 μM) (the values represent the mean+/−one S.D. of n=3 experiments).

Example 10

Primitive high proliferative potential colony forming cells (HHP-CFC) in an adherent layer in culture are usually in a quiescent state. This long term culture (LTC) is established seven to ten days after initiation of the LTC. The cells may be stimulated to proliferate by the addition of fresh medium. Both BFU-E (burst forming unit—erythroid precursor) cells and CFU-GM (colony forming unit—granulocyte-monocyte common precursor) cells of LTC may be maintained in a quiescent state by the mesenchymally derived stromal cells in an adherent layer, but can be reversibly stimulated into the cycle by the addition of fresh media. The ability of CXCR4 agonists such as SDF-1 and SDF-1 polypeptides to overcome this activation may be determined by adding it to the LTC during the medium change. Rapidly dividing cells will accumulate proportionally more of a cytotoxic agent, such as radioactive thymidine, and as a result are preferentially killed.

The results depicted in Table 7 illustrate the ability of SDF-1, and SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809) and SDF-1(1-14)-(G)4-SDF-1(55-67) acid (SEQ ID NO:806) to repress the proliferation of clonogenic erythroid and granulopoitic progenitors (which differentiate into erythrocytes, platelets, monocytes/macrophages and neutrophils) in an in vitro LTC-IC (long-term culture-initiating cells) assay.

TABLE 7 Effect of SDF-1 and SDF-1 agonists on the cycling of primitive progenitors in the adherent layer of human LTC. % CELL KILLED after 3H-Thymidine Treatment Dose Primitive BFU-E Primitive CFU-GM None 48 +/− 4  44 +/− 3  SEQ ID NO: 806 1 μg/ml 24 +/− 6  22 +/− 7  10 μg/ml  0 +/− 2 0 +/− 0 SDF-1 1 μg/ml 4 +/− 3 5 +/− 4 SEQ ID NO: 809 1 μg/ml 2 +/− 4 0 +/− 3

To obtain the results set out in Table 7, clonogenic erythroid (BFU-E) and granulopoietic (CFU-GM) progenitors were assayed in methylcellulose cultures. Adherent cells were treated with fresh medium alone (as control) or with the indicated CXCR4 agonist (10 μg/ml SDF-1, SEQ ID NO:809 or SEQ ID NO:806). Dishes were harvested three days later and 3H-thymidine suicide assays performed on the progenitor cells in the adherent layer to determine the proportion of cells killed as a result of accumulation of cytotoxic 3H-thymidine, where the difference between the cells in the control and the number of cells remaining represent the cells killed.

FIG. 7 illustrates that feeding cultures with SDF-1 in conjunction with media changes results in significantly reduced cell mortality of hematopoietic cells when the cells are challenged with an agent that is preferentially cytotoxic to dividing cells, in which circles represent BFU-E cells (burst forming unit-erythroid precursors), and squares represent CFU-GM cells (colony forming unit-granulocyte-monocyte common precursor). FIG. 8 shows that a similar concentration dependent effect may be obtained with SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/D24-cyclic amide (Compound A) (SEQ ID NO:809) and SDF-1(1-9)2 (Compound J) (SEQ ID NO:802). Together, FIGS. 7 and 8 illustrate that the SDF-1 polypeptide and SDF-1 peptide analogs repress the cyclic activation of the BFU-E and CFU-GM progenitor stem cells in the adherent layer of LTC.

Example 11

FIGS. 9 and 11 show the efficacy of CXCR4 agonists such as SDF-1 and SDF-1 analogues in repressing the proliferation of human progenitor cells in an in vivo engraftment model.

In FIG. 9, the cycling status of mature and primitive colony forming cells (CFU-GM; colony forming unit-granulocyte-monocyte precursor, BFU-E; burst forming unit-erythroid precursor; LTC-IC, long-term culture initiating cell) in the suspension of CD34+ cells isolated from the marrow of transplanted NOD/SCID mice was determined by assessing the proportion of these progenitors that were inactivated (killed) by short term (20 min) or overnight (16 hour) exposure of the cells to 20 μg/ml of high specific activity 3H-thymidine (values represent the mean+/−the S.D. of data from up to four experiments with up to four mice per point in each). Significant in the results described in FIG. 9 is the observation that the analogs Compound A/SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809) and Compound L/SDF-1(1-14)-(G)4-SDF-1(55-67) acid (SEQ ID NO:806) are as effective as native SDF-1 at inhibiting the proliferation of “primitive” human progenitor cells, as measured by the reduction of cells killed by exposure to high specific activity 3H-thymidine (which only affects proliferating cells).

Example 12

SDF-1 enhances the detectability of colony regenerating units (CRU) regenerated in NOD/SCID mice transplanted with human fetal liver cells (FIG. 10). Three to four NOD/SCID mice per group were sublethally irradiated and injected with human cells, in this case 107 light density fetal liver cells, and the mice then maintained for an interval of 2.5-3 weeks. As indicated, each group was then given 2 daily injections of either 10 μg of SDF-1, or an equivalent volume of control medium, and all mice were then sacrificed one day after the second injection. The bone marrow cells from each group were then pooled, and an aliquot removed for FACS analysis and overnight 3H-thymidine suicide assays to measure the cycling activity of the human CFC and LTC-IC (long term culture initiating culture) present. The remainder of the cells was injected into groups of 3-6 secondary recipients. These animals were then sacrificed 6 to 8 weeks later and their bone marrow removed and analyzed for the presence of human cells.

This example describes a secondary engraftment. When the bone marrow of the secondary recipients was evaluated, a considerable difference was observed in the level of human cells present in recipients of cells from the different groups of primary mice. As shown in FIG. 10, for SDF-1-injected mice, a far greater number of all types of human cells assessed was found in the marrow of the secondary recipients that had received marrow from primary mice treated with either SDF-1 by comparison to recipients of cells from media injected control primary mice.

Example 13

This example illustrates the effect of CXCR4 agonists such as SDF-1 and SDF-1 polypeptide analogs on the engraftment of human cells in human fetal liver transplanted NOD/SCID mice (FIG. 11). As shown in this figure, there was a lack of short-term effect of CXCR4 agonists on the frequency of different human cells present in NOD/SCID mice. In these experiments, 6 to 8 weeks post-transplanted mice were injected two times, one day apart with the test compound (SDF-1, Compound A/SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809) or Compound L/SDF-1(1-14)-(G)4-SDF-1(55-67) acid (SEQ ID NO:806)) and sacrificed one day later. The frequency of the phenotypically defined human hematopoietic cells detected in the long bones (tibias and femurs) of mice was determined. Administration of 0.5 mg/kg of SDF-1 had no significant effect on the number of CD45/71, CD19/20, or CD34 cells, nor on the CFC or LTC-IC. In addition, none of the human cell types were detectably affected by this schedule of CXCR4 agonist administration. This data, coupled with that of FIGS. 9 and 10, indicates that SDF-1, SDF-1 analogs and other CXCR4 agonists may effectively augment secondary engraftment of human progenitor cells.

Example 14

This example illustrates the effect of an SDF-1 polypeptide analog represented by SEQ ID NO:809 (10 mg/kg, identified as Compound A in FIG. 12) on the recovery of leukocytes following myeloablative chemotherapy with Ara-C (300 mg/kg). In the experiment described in the example, C3Hhen mice (female) were treated with 500 mg/kg Ara-C for two cycles—on days 0 and 10. During the second cycle of Ara-C dosing, Ara-C treated mice were injected with 10 mg/kg Compound A each day. A control was conducted with animals treated with Ara-C alone. Blood was collected from the tail vein into heparin-containing tubes at the onset of the experiment, and one day before every day following the second Ara-C dose. A total leukocyte count was determined. As shown in the graph of FIG. 12, the CXCR4 agonist Compound A acted to inhibit the cytotoxic effects of Ara-C and to sustain a higher level of leukocytes, illustrating the reversal of myelosuppressive effects of a chemotherapeutic regimen in vivo.

Example 15

This example illustrates the effect of an SDF-1 polypeptide analog Compound A/SDF-1(1-14)-(G)4-SDF-1(55-67)-Lys20/Glu24-cyclic amide (SEQ ID NO:809, 1 mg/kg) on the recovery of leukocytes following myeloablative chemotherapy with Ara-C (500 mg/kg) compared to G-CSF (Neupogen®) (FIG. 13). C3Hhen mice (female) were treated with 500 mg/kg Ara-C for two cycles—on days 0 and 10. During the second cycle of Ara-C dosing, Ara-C treated mice were injected with 10 mg/kg Compound A, 10 mg/kg Neupogen®, alone or together (on days −1, 0, and 1 to 3), with controls receiving no drug. Blood was collected from the tail vein into heparin-containing tubes at the onset of the experiment, and one day before and 1, 7 and 12 days following the second Ara-C dose. A total white blood cell count was obtained. The results in this example indicates that not only does treatment with Compound A enhance the recovery of white blood cells following myeloablative chemotherapy with Ara-C, co-treatment with the SDF-1 polypeptide analog and G-CSF (Neupogen®) resulted in a greater recovery compared the animals treated with G-CSF alone during the early treatment phase. Furthermore, the recovery following treatment with the SDF-1 polypeptide analog was sustained compared to the G-CSF treated animals.

FIG. 14 depicts the results of an experiment conducted under identical conditions, but the growth (increase in leukocyte count) relative to the number of cells counted in animals treated with Ara-C alone is illustrated. By twelve days following Ara-C administration, an approximately 7.5-fold increase in leukocytes was observed in mice treated with Compound A relative to animals treated with Ara-C alone, compared to 180% obtained in animals treated with Neupogen®.

Example 16

Table 8 shows the effect of the CXCR4 agonist, Compound A (SEQ ID NO:809), on the mobilization of leukocytes (neutrophils) in mice injected intravenously. Compound A was injected intravenously into Balb/C mice at 25 mg/kg. To obtain the data in Table 8, blood was collected through cardiac puncture and counted for the increase in white blood cells, and platelets.

TABLE 8 Effect of the SDF-1 agonist, Compound A, on the mobilization of leukocytes (neutrophils) in mice. Neutrophils Treatment day (109/l) Lymphocytes (109/l) Platelets (109/l) Day 0 0.968 +/− 0.311 4.78 +/− 0.88 1099 +/− 50  (untreated) Day 2 3.159 +/− 0.761  3.15 +/− 1.075 1044 +/− 65  (Compound A treated) Day 3 3.209 +/− 0.735 3.371 +/− 1.113 977 +/− 152 (Compound A treated) Day 5 1.592 +/− 0.961 5.325 +/− 0.771 882 +/− 88  (Compound A treated) Day 5 0.893 +/− 0.371 6.540 +/− 0.970 937 +/− 169 (untreated) Day 8 2.513 +/− 2.733 4.072 +/− 1.386 1111 +/− 124  (Compound A treated)

In Table 8, the Compound A peptide is represented by the structure set forth in SEQ ID NO:809.

These results demonstrate that CXCR-4 agonists, such as Compound A (SEQ ID NO:809), may be used to mobilize neutrophils (for example in patients undergoing chemotherapy to facilitate blood cell recovery). In this example, intravenous injection of the CXCR-agonist may facilitate the creation of an artificial chemotactic gradient, which may facilitate an immune response in the target tissue (in this case, blood). The gradient is established when the active therapeutic compound has pharmacokinetic characteristics that facilitate an appropriate residence time in the tissue into which the compound is administered, coupled with an appropriate susceptibility to degradation in vivo so that the concentration of the compound decreases away from the target tissue. In alternative embodiments, the invention therefore provides methods of treating a subject comprising administering to a target tissue a labile chemokine receptor agonist or antagonist so as to create an artificial chemotactic gradient. The agonist or antagonist may for example have a plasma half life of not more than 2 hours, as is the case with Compound A, or not more than 1, 3, 4, or 5 hours in alternative embodiments. One aspect of the invention provides a route of therapeutic chemokine administration which establishes an essentially uniform dosage of the chemokine receptor ligand in the target tissue, with a decreasing dosage of the chemokine radiating from the target tissue. For example, an inhaled aerosol formulation may be used to administer a labile chemokine receptor agonist or antagonist to the lung epithelium.

Example 17

Alternative embodiments of Compound A-like (SEQ ID NO:809) and Compound K-like (SEQ ID NO:803) SDF-1 analogs may include CXCR4 agonist peptides such as

SDF-1-derived Glu24/Lys28-cyclic amide (Compound A-like) compounds having the formula

(SEQ ID NO:807) [RNH-Lys]Xaa1-Val-Ser-Xaa2-Ser-Tyr-Arg-Cys-Pro- Cys-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2; and

SDF-1-derived Lys20/Glu24-cyclic acids (Compound K-like) compounds having the formula

(SEQ ID NO:808) [RCONH-Lys]Xaa1-Val-Ser-Xaa2Ser-Tyr-Arg-Cys-Pro- Cys-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-NH2.

In the foregoing peptides, R is a substituent that may for example be a hydrogen, alkyl, aryl or polyethyleneglycol (PEG) moiety; Xaa1 is an amino acid that may for example be either an L-Proline or a D-Proline moiety; Xaa2 is an amino acid that may for example be either a L-Leucine or a D-Leucine moiety; and [linker] is a moiety providing a covalent attachment between the N and C terminal portions of the peptides, such as a linking moiety having 4 glycines or NH2—(CH2)n—COOH (n=0-20). Examples of such compounds are shown in FIG. 17.

Example 18

This example illustrates the efficacy of SDF-1 chemokine analog, Compound B (SEQ ID NO:810), in mobilization of hematopoietic progenitor cells into the circulation in a mouse model. A dose response curve is shown in FIG. 16. Briefly, female Balb/c mice of 18-21 g body weight were injected intravenously with 2.5, 10 or 25 mg/kg of Compound B (SEQ ID NO:810). The control consists of animals injected with saline. After 10 min, 1 h, 4 h and 24 h, blood was collected by cardiac puncture. Erythrocytes were lysed using ice cold ammonium chloride at nines the volume of the blood. After two washes with Iscove's Modified Dulbecco's Medium (Invitrogen, Burlington, Ontario, Canada) containing 2% fetal bovine serum (Invitrogen), an aliquot of cells were mixed with two times the volume of 3% acetic acid and the concentration of cells counted using a hemocytometer. The remaining cells were diluted to 1.5×106 cells/ml with IMDM containing 2% fetal bovine serum. 0.3 ml of cells was mixed with 3 ml MethoCult (Stem Cell Technologies, Vancouver, Canada). 1.1 ml of which was dispensed into each duplicate 35 mm culture dishes. Each pair was placed in a 100 mm petri dish with a third 35 mm dish containing 3 to 4 ml of sterile water and incubated at 37° C. and 5% CO2 in a humidified incubator. After 10-12 days, the number of colony forming unit granulocyte-macrophage (CFU-GM) was counted in each plate and the data expressed as CFU/ml blood. The values in the figure represent the mean+/−one S.D. from a representative experiment. A time and concentration-dependent mobilization of hematopoietic progenitor cells into the circulation is illustrated, indicating the rapid and potent activity of the peptide analog.

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. A method of modulating an activity of a cell having an SDF-1 receptor comprising binding the SDF-1 receptor of the cell with an SDF-1 mimetic consisting of the following structure: (SEQ ID NO:10) RN-HN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-RC; wherein,

RN is an N-terminal modifier that comprises a component selected from a group consisting of hydrogen, poly(ethylene glycol), a biochemical label, a radiolabel, an acyl group, an acetyl group, and an N-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for aminopeptidases;
RC is a C-terminal modifier that comprises a component selected from a group consisting of a hydroxyl group, poly(ethylene glycol), a biochemical label, a radio label, an amido group, and a C-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for carboxypeptidases;
Xaa1, Xaa2, and Xaa3 are each independently selected from a group consisting of (a) any natural amino acid; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, where ZA is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms, cycloalkyl amines, and fused cycloalkyl amines;
and,
the linker is selected from a group consisting of (a) any combination of four natural amino acids; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, wherein ZA is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms that are optionally substituted with a hydroxyl, carboxyl, carbonyl, thiol, amino, amido, imino, or an aromatic group having from 5 to 7 members in the ring; and —(CH2)n—, wherein n is an integer ranging from 9 to 14.

2. The method of claim 1, wherein Xaa1 and Xaa2 are each independently selected from a group consisting of Ala, Cys, and Phe; Xaa3 is selected from a group consisting of Lys and des-Lys; and any combination thereof.

3. The method of claim 1, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:405, SEQ ID NO:406, and variants f400 and f401, wherein the C-terminal portion is cyclized at Lys20 and Glu24.

4. The method of claim 3, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:808 to SEQ ID NO:813, wherein the C-terminal portion is cyclized at Lys20 and Glu24.

5. The method of claim 1, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:307 and variant f300, wherein the C-terminal portion is cyclized at Glu24 and Lys28.

6. The method of claim 5, wherein the SDF-1 mimetic is selected from group consisting of SEQ ID NO:803 and SEQ ID NO:807, wherein the C-terminal portion is cyclized at Glu24 and Lys28.

7. The method of claim 1, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:801 and SEQ ID NO:806.

8. The method of claim 1, wherein the cell is a hematopoietic cell selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils.

9. The method of claim 1, wherein the binding reduces the rate of multiplication of the cell.

10. The method of claim 1, wherein the cell is a quiescent cell, and the binding represses the activation of the quiescent cell.

11. A method of modulating an activity of hematopoietic cells in a subject comprising administering an effective amount of a composition comprising an SDF-1 mimetic to the subject, wherein the SDF-1 mimetic consists of the following structure: (SEQ ID NO:10) RN-HN-Xaa3-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro- Xaa2-Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu- Tyr-Leu-Glu-Lys-Ala-Leu-Asn-RC; wherein,

RN is an N-terminal modifier that comprises a component selected from a group consisting of hydrogen, poly(ethylerie glycol), a biochemical label, a radiolabel, an acyl group, an acetyl group, and an N-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for aminopeptidases;
RC is a C-terminal modifier that comprises a component selected from a group consisting of a hydroxyl group, poly(ethylene glycol), a biochemical label, a radiolabel, an amido group, and a C-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for carboxypeptidases;
Xaa1, Xaa2, and Xaa3 are each independently selected from a group consisting of (a) any natural amino acid; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, where ZA is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms, cycloalkyl amines, and fused cycloalkyl amines;
and,
the linker is selected from a group consisting of (a) any combination of four natural amino acids; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, where ZA is selected from a group consisting of saturated and unsaturated aliphatics and heteroaliphatics consisting of 20 or fewer carbon atoms that are optionally substituted with a hydroxyl, carboxyl, carbonyl, thiol, amino, amido, imino, or an aromatic group having from 5 to 7 members in the ring; and —(CH2)n—, wherein n is an integer ranging from 9 to 14.

12. The method of claim 11, wherein Xaa1 and Xaa2 are each independently selected from a group consisting of Ala, Cys, and Phe; and Xaa3 is selected from a group consisting of Lys and des-Lys.

13. The method of claim 11, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:405, SEQ ID NO:406, and variants f400 and f401, wherein the C-terminal portion is cyclized at Lys20 and Glu24.

14. The method of claim 13, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:808 to SEQ ID NO:813, wherein the C-terminal portion is cyclized at Lys20 and Glu24.

15. The method of claim 11, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:307 and variant f300, wherein the C-terminal portion is cyclized at Glu24 and Lys28.

16. The method of claim 15, wherein the SDF-1 mimetic is selected from group consisting of SEQ ID NO:803 and SEQ ID NO:807, wherein the C-terminal portion is cyclized at Glu24 and Lys28.

17. The method of claim 11, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:801 and SEQ ID NO:806.

18. The method of claim 11, wherein the administering results in mobilizing the hematopoietic cells.

19. The method of claim 11, wherein the administering results in enhancing recovery of the hematopoietic cells following chemotherapy.

20. The method of claim 19, wherein the enhancing comprises reducing the rate of multiplication of the hematopoietic cells to inhibit the effect of a cytotoxic agent on the hematopoietic cells during the chemotherapy.

21. The method of claim 11, wherein the administering results in enhancing an engraftment of the hematopoietic cells in a second subject.

22. The method of claim 11 further comprising administering a second agent, wherein the administering of the second agent is sequential or concurrent to the administering of the composition comprising the SDF-1 mimetic.

23. The method of claim 22, wherein the second agent comprises G-CSF.

24. The method of claim 11, wherein the hematopoietic cell is selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, or neutrophils.

25. A method of increasing the number of hematopoietic cells circulating in the blood of a subject, wherein the method comprises administering an effective amount of a composition comprising an SDF-1 consisting of the following structure: (SEQ ID NO:405) RN-Lys-Pro-Val-Ser-Leu-Ser-Tyr-Arg-Xaa1-Pro-Xaa2- Arg-Phe-Phe-[linker]-Leu-Lys-Trp-Ile-Gln-Glu-Tyr- Leu-Glu-Lys-Ala-Leu-Asn-RC; wherein,

RN is an N-terminal modifier that comprises a component selected from a group consisting of hydrogen, poly(ethylene glycol), a biochemical label, a radiolabel, an acyl group, an acetyl group, and an N-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for aminopeptidases;
RC is a C-terminal modifier that comprises a component selected from a group consisting of a hydroxyl group, poly(ethylene glycol), a biochemical label, a radiolabel, an amido group, and a C-terminal modifier capable of reducing the ability of the SDF-1 mimetic to act as a substrate for carboxypeptidases;
Xaa1 and Xaa2 are each independently selected from a group consisting of Ala, Cys, and Phe;
and,
the linker is selected from a group consisting of (a) any combination of four natural amino acids; and (b) any non-natural amino acid having the structure H2N-ZA-COOH, where ZA is selected from a group consisting of —(CH2)n—, wherein n is an integer ranging from 9 to 14.

26. The method of claim 25, wherein the SDF-1 mimetic is selected from a group consisting of SEQ ID NO:808 to SEQ ID NO:810, wherein the C-terminal portion is cyclized at Lys20 and Glu24.

27. The method of claim 25, wherein the administering mobilizes hematopoietic cells.

28. The method of claim 25, wherein the administering reduces multiplication of the cells and inhibits the effect of a cytotoxic agent on the hematopoietic cells during the chemotherapy.

29. The method of claim 25, wherein the hematopoietic cells are selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, or neutrophils.

30. The method of claim 25 further comprising administering a second agent, wherein the administering of the second agent is sequential or concurrent to the administering of the composition comprising the SDF-1 mimetic.

31. The method of claim 30, wherein the second agent comprises G-CSF.

Patent History
Publication number: 20070275892
Type: Application
Filed: Mar 29, 2006
Publication Date: Nov 29, 2007
Patent Grant number: 7994114
Applicant:
Inventors: Ahmed Merzouk (Richmond), Abdelkrim Habi (Dollard-Des-Ormeaux (Montreal)), Donald Wong (Vancouver), Hassan Salari (Delta)
Application Number: 11/393,769
Classifications
Current U.S. Class: 514/12.000
International Classification: A61K 38/16 (20060101);