Abstract: A method for determining the level of kinase activity or phosphatase activity in a sample without the use of antibodies or radioactive labels is disclosed. The method employs a fluorescently-labeled phosphorylatable reporter peptide that is capable of being cleaved by a protease only when the peptide is in an unphosphorylated state. A change in fluorescence characteristics is an indication that the peptide is cleaved and, therefore, in an unphosphorylated state. Thus, the level of protease cleavage, as measured by the fluorescence change, provides a direct measure of phosphatase activity whereas the level of kinase activity is inversely proportion to the level of protease cleavage. The method is particularly well suited to high throughput screening, for example, for screening compounds which modulate kinase or phosphatase activity.

Abstract: Cyclic to Synthetic pseudopeptide derivatives of osteogenic growth polypeptide (OGP) and OGP(10-14) which are capable of enhancing bone cell proliferation and bone formation. Pharmaceutical composition comprising as active ingredient at least one pseudopeptide derivative of the invention and to the use of these pseudopeptide derivatives in the preparation of a pharmaceutical composition for stimulating the formation of osteoblastic or fibroblastic cells, enhancing bone formation in osteopenic pathological conditions, repairing fractures, healing wounds, grafting of intraosseous implants, reversing bone loss in osteoporosis and other conditions requiring enhanced bone cells formation.

Abstract: The present invention provides peptides and peptidomimetics corresponding to part or to the entirety of the region encompassed by residues 360–386 of human p53, said peptides and peptidomimetics characterized by the ability to activate DNA binding of wild-type p53 and of select tumor-derived p53 mutants. Pharmaceutical compositions of the compounds of the invention and methods of using these compositions therapeutically are also provided.

Abstract: The invention provides a pharmaceutical agent delivery composition comprising: (i) a transport polymer comprising a linear or branched peptide having from about 10 to about 300 amino acid residues, having from about 5 to 100% histidine residues, and optionally having from 0 to about 95% non-histidine amino acid residues; (ii) at least one pharmaceutical agent; and optionally (iii) one or more intracellular delivery components in association with the transport polymer. The invention also provides methods for using such composition to deliver the pharmaceutical agent to the interior of cells.

Abstract: The invention provides isolated HLA DRB1*15-binding peptides consisting of the amino acid sequence set forth as SEQ ID NO:7 with 0–10 amino acids added to either or both ends of the amino acid sequence set forth as SEQ ID NO:7, and an endosomal targeting signal comprising an endosomal targeting portion of human invariant chain Ii or LAMP-1.

Abstract: The invention relates to modified and truncated forms of the membrane transport vector penetratin. Such truncated forms include 7-mer peptides that may in themselves include further variation.

Abstract: The present invention provides, among other things, a polypeptide, and a pharmaceutically acceptable salt thereof, that inhibits the binding of IL-6 ligand with IL-6 receptor under physiological conditions, a nucleic acid that encodes such a polypeptide and can be expressed in a cell, a nucleic acid that comprises or encodes an antisense nucleic acid molecule or a ribozyme that is specific for such a polypeptide, an antibody that is specific to such a polypeptide, an anti-antibody thereto, a composition comprising such a polypeptide, nucleic acid, antibody or an anti-body and a carrier therefor, a composition comprising a solid support matrix to which is attached an above-described polypeptide or an anti-antibody to a specified polypeptide sequence, a method of prophylactically or therapeutically inhibiting IL-6 signaling in a mammal in need thereof, a mammal in need thereof, and a method of removing IL-6 ligand from a bodily fluid of an animal.

Abstract: The present invention relates to macrocyclic depsipeptides, including didemnin analogs and fragments thereof, which are useful as anti-cancer agents and for other purposes. The invention includes numerous didemnin analogs and fragments and methods of making them. Methods of using these compounds as inhibitors of protein synthesis, cell growth, and tumorigenesis and as enhancers of apoptosis are also provided.

Abstract: A stabilized pharmaceutical composition in lyophilized form comprising: a cyclic polypeptide compound represented by the general formula (I): wherein R1 is a hydrogen atom or an acyl group and R2 and R3 are, the same or different, a hydrogen atom or a hydroxyl group, or a salt thereof and the stabilizer.

Abstract: The present invention relates to compositions comprised of a peptide ligand or derivatives thereof that are capable of specific binding to the high affinity receptor-1 of vascular endothelial growth factor (VEGF) and structure similar receptors. The invention further provides a peptide ligand or derivatives thereof that are capable of inhibiting angiogenesis induced by VEGF. The present invention also provides a method for treatment or diagnosis of disease associated with angiogenesis in a patient in need of therapy comprising administering to the patient an effective amount of the pharmaceutical composition of the present invention and a pharmaceutical acceptable carrier.

Abstract: The present invention provides novel identification polypeptides containing multiple copies of an antigenic domain joined in tandem to provide increased sensitivity for the detection and purification of target peptides, a cleavable linking sequence and optionally a spacer domain. Further provided are hybrid polypeptide molecules composed of an identification polypeptide and a target peptide which are produced by recombinant DNA technology and purified using affinity chromatography using one or more ligands. Accordingly, also provided are DNA expression vectors containing DNA encoding for identification polypeptides and methods for using such identification polypeptides for the purification of target peptides. Also provided are methods of constructing DNA vectors encoding the novel identification polypeptides and DNA expression vectors encoding the identification polypeptides linked to a target peptide.

Abstract: The present invention relates to peptide compounds that are agonists of the erythropoietin receptor (EPO-R). The invention also relates to therapeutic methods using such peptide compounds to treat disorders associated with insufficient or defective red blood cell production. Pharmaceutical compositions, which comprise the peptide compounds of the invention, are also provided.

Abstract: The present invention relates to a purified or isolated polynucleotide encoding human CIDE B protein, the regulatory nucleic acids contained therein, polymorphic markers thereof, and the resulting encoded protein, as well as to methods and kits for detecting this polynucleotide and this protein. The present invention also pertains to a polynucleotide carrying the natural regulatory regions of the CIDE B gene which is useful, for example, to express a heterologous nucleic acid in host cells or host organisms as well as functionally active regulatory polynucleotides derived from said regulatory regions.

Abstract: Method for reducing the level and/or activity of a target protein in a eukaryotic cell via activation of ubiquitination of the target protein wherein the cell is contacted with the compound having a ubiquitination recognition element covalently linked to a target protein binding element. The ubiquitination and recognition element can bind to either the E3 or E2 elements of the ubiquitination system and the target protein binding element is able to bind specifically to the target protein. The target protein binding element has a molecular weight of less than 30,000 and has a binding affinity for the target protein greater than 105M31 1.

Abstract: The invention provides a branched transport polymer characterized as having at least 10 amino acids and a ratio of histidine to non-histidine amino acids greater than 1.5, said branched transport polymer comprising one or more backbones, one or more terminal branches, and optionally, one or more non-terminal branches. The branched transport polymer may be associated with a pharmaceutical agent to form a pharmaceutical agent delivery composition useful for in vivo therapies based on local injection.

Abstract: The present invention generally relates to the detection, treatment or prevention of disease states. Specifically, the present invention relates to the detection, treatment or prevention of amyloidosis or amyloid-associated diseases. The present invention further comprises methods and compositions comprising therapeutic vaccines, antisera and molecular constructs, comprising expression vectors and fusion proteins encoded therein.

Abstract: The present invention relates to tamandarin and didemnin analogs which have a deoxo-proline residue or a dehydro-proline residue in their structure. These analogs are useful as anti-cancer agents and for other purposes. Methods of making these analogs and methods of using them as inhibitors of protein synthesis, cell growth, and tumorigenesis and as enhancers of apoptosis are also provided.

Abstract: The present invention relates to reduced FK228 of the formula (I) wherein R1 and R2 are the same or different and each is a hydrogen atom or a thiol-protecting group, or a salt thereof, and a histone deacetylase inhibitor containing this compound, an expression potentiator and a reactivation promoter of a transgene, and pharmaceutical agents containing them as active ingredients. The reduced FK228 or a salt thereof has a strong histone deacetylase inhibitory activity and this compound can be used for the prophylaxis or treatment of various diseases, in which histone deacetylation is involved, and for the gene therapy of such diseases.

Abstract: The present invention relates to MMP regulators that comprise new synthetic peptides, that comprise amino acid sequences structurally similar to those of MMP binding region of TIMPs, coupled to zinc chelators. The invention also relates to methods for making these MMP regulators and their use for the treatment of chronic and acute wounds and for the treatment of angiogenesis-associated diseases.

Abstract: Peptide analogs of neurotensin are disclosed which are resistant to enzymatic degradation and which retain high binding affinity for neurotensin receptors. Pharmaceutical compositions of these compounds are useful for diagnostic and therapeutic purposes.

Abstract: The present invention relates to analogues of peptides from lipopolysaccharide-binding protein (LBP) region whose primary sequence have been substituted at particular amino acid sites to obtain effective binding to, and neutralization of, lipopolysaccharide (LPS).

Abstract: The invention concerns in particular novel peptides and polypeptides comprising at least the following sequence in amino acids: -W-S-A1-C-S-A2-C-G- in which A1 and A2 are amino acid sequences comprising 1 to 5 amino acids, useful as medicines in therapeutic treatments involving the regeneration of the nervous system cells, for treating neuroblastomas, and also useful as additives in the culture of nervous cells.

Abstract: Isolated and purified chemokine peptides, variants, and derivatives thereof, as well as chemokine peptide analogs, are provided.

Abstract: Disclosed are compounds for SH2 domain binding inhibition. For example, disclosed is a compound of formula (I) wherein R1 is a lipophile; R2, in combination with the phenyl ring, forms a phenylphosphate mimic group or a protected phenylphosphate mimic group; R3 is hydrogen, azido, amino, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, or alkylcarbonylamino, wherein the alkyl portion of R3 may be optionally substituted with a substituent selected from the group consisting of halo, hydroxy, carboxyl, amino, aminoalkyl, alkyl, alkoxy, and keto; R6 is a linker; AA is an amino acid; and n is 1 to 6; or a salt thereof. Also disclosed are a pharmaceutical composition, a method for inhibiting an SH2 domain from binding with a phosphoprotein and a method of treating breast cancer.

Abstract: The present invention relates to a method of simultaneously identifying and determining the levels of expression of cysteine-containing proteins in normal and perturbed cells, a method for proteomic analysis, a process for preparing fusion proteins, and compounds of Formula II and III: (II) Acyl-NH—X-[Epitope Tag Site]A-Y-[Protease Cleavage Site]-Z-Link (III) Acyl-NH—X-alk-O-Ph-CH2—Z-Link and reagents related thereto.

Abstract: The present invention provides a cyclic peptide comprising the structure: wherein X is selected from the group consisting of an amino acid, an amino acid analog, a peptidomimetic and a non-amide isostere, Z is selected from the group consisting of a synthetic amino acid and a biosynthetic amino acid, R is selected from the group consisting of oxygen, nitrogen, sulfur and carbon, n is 0 to 10 and y is 1 to 10. The present invention also provides a cyclic peptide comprising the amino acid sequence of NH2—X(n)-Z-X(y)—COOH and a cyclic bond between the Z residue and COOH other than a thioester bond, wherein X is selected from the group consisting of an amino acid, an amino acid analog, a peptidomimetic and a non-amide isostere, Z is selected from the group consisting of a synthetic amino acid and a biosynthetic amino acid, n is 0 to 10 and y is 1 to 10. Methods of preparation including a cyclization protocol, and methods of use of the cyclic peptides of the invention are also disclosed.

Abstract: The invention provides a variety of therapeutic uses for CXCR4 antagonists. In various embodiments. CXCR4 antagonsits may be used as therapeutically as follows, or to manufacture a medicament for such therapeutic treatments: reducing interferon gamma production by T-cells, treatment of an autoimmune disease, treatment multiple sclerosis, treatment of cancer, inhibition of angiogenesis. The invention provides corresponding methods of medical treatment, in which a therapeutic dose of a CXCR4 antagonist is administered in a pharmacologically acceptable formulation. Accordingly, the invention also provides therapeutic compositions comprising a CXCR4 antagonist and a pharmacologically acceptable excipient or carrier. The CXCR4 antagonists for use in the invention may be peptide compounds comprising a substantially purified peptide fragment, modified fragment, analogue or pharmacologically acceptable salt of SDF-1.

Abstract: The present invention relates to the use of at least a non-peptidyl compound as a biological modulator of insulin activity or insulin-related activity, which compound possesses ionic and hydrophobic chemical moieties spatially located so as to mimic at least an ionic and hydrophobic amino acid residue of insulin, which amino acids are associated with the binding of insulin to its receptor.

Abstract: Compositions and methods of using compositions with a nuclear targeting peptide containing a nonclassical nuclear localization signal to deliver selected molecules to the nucleus of eukaryotic cells are provided. The compositions are useful for gene transfer.

Abstract: The present invention provides a basic amino acid derivative represented by the formula (1): The present invention also provides a method of making a gelled product by employing the aforementioned compound, as well as a gel, perfumery, and/or cosmetic containing the same.

Abstract: This invention is the discovery of novel specific epitopes and antibodies associated with long term survival of HIV-1 infections. These epitopes and antibodies have use in preparing vaccines for preventing HIV-1 infection or for controlling progression to AIDS.

Abstract: A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has at least two of the glycosylation sites proximal to the CD4 binding site or chemokine receptor site altered so that the alteration prevents glycosylation at that site or where glycosylation sites distal to these sites have been derivatized with a molecular adjuvant, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has both changes. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp 120.

Abstract: The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from Streptococcus pneumoniae. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising unique fragment of at least 10 nucleotides of the 37-kDa protein. Additionally, multiple antigenic peptides that provide protection against S. pneumoniae challenge are provided. These multiple antigen peptides comprise the peptides that immunospecifically bind to the monoclonal antibodies. Also provided are vaccines comprising such immunogenic peptides, and methods of conferring protective immunity against Streptococcus pneumoniae infection by administering therapeutic composition comprising the immunogenic peptides of the invention.

Abstract: The present invention discloses a family of cyclic peptide monomers and supramolecular cyclic peptide structures comprising chromophore residues which possess electronic and electro-optic properties for producing molecular scale electronic and photonic devices made from such materials. More particularly, this invention provides for cyclic peptide nanotube structures formed from a plurality of stacked cyclic peptides comprising chromophore residues that provide molecular scale electronic conductivity and non linear optical behavior. The stackable cyclic peptide is represented by the general formula where R1 is H, CH3 or alkyl; where at least one R2 is a chromophore; where R3 is H, CH3 or a polar or non-polar organic functional group used for controlling peptide stacking and solubility; where n equals 1 or 2; where m equals 4 or 6; and where a first adjacent amino acid residue has an ?-carbon chirality of L and a second adjacent amino acid residue has an ?-carbon chirality of D.

Abstract: The present invention relates to the use of 24-membered cyclodepsipeptides of the formula (1) in which R1 and R2 are as defined in the description, for controlling animal pests in veterinary medicine, hygiene, agriculture, forests and in the protection of materials, to pesticides comprising these depsipeptides and to novel depsipeptides of the formula (1).

Abstract: The present invention concerns peptides as inhibitors of the binding of urokinase to the urokinase receptor. These peptides, which are preferably cyclic, are suitable as pharmaceutical agents for diseases that are mediated by urokinase and its receptor.

Abstract: The invention includes a method for harvesting a polypeptide produced by a host cell, wherein the polypeptide has not undergone intracellular posttranslational modification, such as dehydration of a serine or a threonine, and/or thioether bridge formation. The invention also includes a method for producing thioether-containing peptides and dehydroalanine/dehydrobutyrine-containing.peptides, wherein thioether rings may be formed extracellularly.

Abstract: Cyclic depsipeptides represented by the formula wherein: R is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15-carbon atoms; A, B, D, E and F independently each other are alanine, valine, leucine, isoleucine, phenylalanine, etc.; W and Z independently each other are aspartic acid, asparagine, glutamic acid or glutamine; and m and n independently each other is 0 or 1, or pharmacologically acceptable salts thereof. The present compounds are prepared according to a method conventionally used in peptide synthesis. The present compounds are useful as an agent for promoting the production of apolipoprotein E, a therapeutic agent for neurologic damages, a therapeutic agent for dementia, an agent for inhibiting the production of apolipoprotein B, an agent for promoting the production of apolipoprotein A1 or a therapeutic agent for hyperlipemia.

Abstract: The present invention relates to novel Aerothricins represented by the Formula (I), and pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition comprising an Aerothricin of the Formula (I) and a pharmaceutically acceptable carrier. Furthermore, the present invention relates to the use of such Aerothricins for the preparation of medicaments, as well as to processes for the preparation of the Aerothricins of the Formula (I).

Abstract: Assays employing fibronectin-depleted substrates are described to identify invasion inducing agents. Such agents are useful for in vivo wound healing, including but not limited to deep wounds and chronic wounds.

Abstract: The invention concerns a compound exhibiting an anti-heparin activity, of formula ZBm?(AXA)xBn?(AXA)yBo(AXA)zBp, the diagnostic reagents comprising it and the use of said compound in an in vitro diagnostic test of a medicine for anti-heparin activity.

Abstract: A living body component in a sample derived from a living body can be rapidly and accurately measured by reacting the sample with a reagent comprising a combined product of an affinity substance and a polypeptide having at least three acid residues derived from a strong acid, separating the resulting complex by a method applying negative change such as using an anion-exchanger, and determining the amount of the analyte to be measured, on the basis of the amount of the complex or free combined product.

Abstract: Depsipeptides and congeners thereof are disclosed having the following structure: wherein m, n, p, q, X, R1, R2 and R3 are as defined herein. These compounds including FR901228, have activity as, for example, immunosuppressants, as well as for the prevention or treatment of patients suffering or at risk of suffering from inflammatory, autoimmune or immune system-related diseases including graft-versus-host disease and enhancement of graft/tissue survival following transplant. Also provided are methods for inhibiting lymphocyte activation, proliferation, and/or suppression of IL-2 secretion.

Abstract: The present invention includes polymeric transport systems corresponding to the formula: wherein: R31 is a linear or branched polymer residue; Y10 and Y11 are independently O, S, or NR40; X2 is O, S or NR41; R32-35, R37-41, R50 and R51 are independently selected among hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls; a, b and e are each independently selected positive integers; L is an amino acid residue or a bifunctional linker; X3 is wherein Y12 and Y13 are independently O, S, or NR41; Z is a bond, a moiety that is actively transported into a target cell, a hydrophobic moiety or combinations thereof; D1 and D2 are OH, a residue of a hydroxyl, a residue of an amine-containing moiety or a leaving group; and y1 and y2 are independently selected positive integers.

Abstract: The present invention relates to novel cyclic or constrained acyclic compounds which modulate the activity of G protein-coupled receptors and are useful in the treatment of conditions mediated by G protein-coupled receptors, for example, inflammatory conditions.

Abstract: The present invention provides a multimeric complex of at least two chimeric molecules, wherein the chimeric molecules comprise an immunoglobulin constant region element and two MHC elements wherein each MHC element is associated with a peptide, and wherein the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker. Methods of making and using the multimeric complexes are also provided.

Abstract: A therapeutical vaccine complex having activity specific for Helicobacter bacteria as well as non-specific immunomodulation activity for regulating the natural defenses of the body. The drug is also useful for preventing relapses, particularly in cases of resistance to conventional treatment. The drug essentially consists of RNA, selective membrane fractions of microbial germs, particular amino acid sequences, sodium chloride and a steroidal anti-inflammatory in predetermined proportions enabling simultaneous delivery of antibiotics and frenosecretories. Said drug is particularly suitable for treating digestive tract diseases caused by Helicobacter (antral gastritis, duodenal ulcers, gastric ulcers, oesophagitis, hepatitis) and preventing stomach cancer and degenerative infectious MALT (mucosa-associated lymphoid tissue) lymphoma, as well as coronary diseases directly or indirectly dependent on Helicobacter infections.

Abstract: The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

Abstract: A stabilized pharmaceutical composition in lyophilized form comprising: a cyclic polypeptide compound represented by the general formula (I): wherein R1 is a hydrogen atom or an acyl group and R2 and R3 are, the same or different, a hydrogen atom or a hydroxyl group, or a salt thereof and the stabilizer.

Abstract: Novel cyclodepsipeptide intermediates have been prepared from the A21978 complex and used to synthesize new lipodepsipeptide antibiotics. The three intermediates can be readily derivatized to give new families of antibiotics that have potent antibacterial activity against gram positive bacteria.