Abstract: The present disclosure teaches analogs of human chemokines and methods of using them in the prevention, treatment, and ameliorization of diseases that can benefit from therapeutic angiogenesis. The teachings are generally directed to compositions comprising SDF-1 mimetics, as well as methods that include the use of SDF-1 mimetics to induce neo-vessel formation. The disclosure also teaches articles of manufacture that can be useful in practicing the methods taught herein.

Abstract: The inventive polypeptide is embodied in the form of a similar fragment of the epidermal growth factor of aminoacid ranging from 21 to 31 and capable of efficiently binding with the receptor of the epidermal growth factor as a vector for the directed supply of anticancer agent to tumour cells. The inventive conjugate of said polypeptide contains doxorubicine and has a selective action on cancer tumours and can substantially reduce the resistance of tumour cells with respect to the anticancer agents, the conjugated parts of said agents being binded with the aid of a chemical bond which is unstable in relation to acid hydrolysis. The inventive pharmaceutical composition comprises an efficient quantity of conjugate and a carrier which is fit for intravenous injection. Said invention can be used for medicine for treating cancer patients.

Abstract: A catalytically active peptide comprising an imidazole function in position i flanked by at least one functional group to be amidated in position i+3+4k, where k is an integer equal to or higher than ?1 or in position i?4?4n, wherein n is an integer equal to or higher than 0, characterized in that it also comprises at least one activating group in position i+4+4n or i?3?4n, respectively, wherein n is as above.

Abstract: Methods for forming peptide derivatives using functional moieties and peptide derivatives are provided. Further, methods for using peptide derivatives to form silicon-based composite materials and silicon-based composite materials formed thereby are provided. The silicon-based composite materials may have features on the nanoscale, and the materials may exhibit characteristics derived from the functional moieties on the peptide derivatives. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that is will not be used to interpret or limit the scope or meaning of the claims.

Abstract: Conjugates comprising one or more steroids conjugated with one or more mammalian proteins are disclosed. The conjugates are useful for diagnosis or treatment of solid cancer and hematological malignancies. Further the conjugates exhibit a synergistic action together with a cytoskeleton-acting drug such as Taxol®, which enable the treatment of cancers that otherwise would be non-responsive to Taxol®.

Abstract: The invention provides intermediates and methods that allow for site-specific modification of peptides after synthesis. Accordingly, functional molecules can be selectively linked to a peptide to provide a peptide conjugate having altered biological, chemical, or physical properties. For example, functional molecules (e.g. biophysical probes, peptides, polynucleotides, and therapeutic agents) can be linked to a peptide to provide a peptide conjugate having differing and useful properties. The invention also provides a compound of formula (III): wherein: R6 is a peptide; X is a direct bond or a linking group; R7 is hydrogen, (C1-C6)alkyl, an amino protecting group, or a radical comprising one or more aminooxy groups; Y is a direct bond or a linking group; and D is a functional molecule.

Abstract: Chemically-defined, non-polymeric valency platform molecules and conjugates comprising chemically-defined valency platform molecules and biological or chemical molecules including polynucleotide duplexes of at least 20 base pairs that have significant binding activity for human lupus anti-dsDNA autoantibodies.

Abstract: This invention characterizes the specific peptide fragment derived from specially prepared zinc charged fetuin and a method of preparation thereof, wherein the fragment was found to contain an apoptosis-inducing activity. Specifically, the amino acid sequence of this peptide is His-Thr-Phe-Met-Gy-Val-Val-Ser-Leu-Gly (SEQ ID NO: 3) and correlates to amino acid no. 300-309 of bovine fetuin, referred to herein as Fetuin Peptide Fragment (FPF 300-09). FPF 300-09 strongly induced apoptosis in LNCaP (prostate cancer) and HT-29 (colon cancer) cells without affecting CCD 18 Co (normal colon) cells. The in vitro tissue culture study demonstrated that the FPF 300-09 is more potent than the parent molecule (full-length zinc charged fetuin) in inducing apoptosis. FPF 300-09 has a LD50 of 0.3-0.4 ?M, while the LD50 for zinc-charged fetuin is 3-10 ?M.

Abstract: This invention characterizes the specific peptide fragment derived from specially prepared zinc charged fetuin and a method of preparation thereof, wherein the fragment was found to contain an apoptosis-inducing activity. Specifically, the amino acid sequence of this peptide is His Ala Phe Ser Pro Val Ala Ser Val Glu, SEQ ID NO:5. The peptide induced apoptosis in LNCaP (prostate cancer) and HT-29 (colon cancer) cells without affecting CCD 18 Co (normal colon) cells. The in vitro tissue culture study demonstrated that the peptide is more potent than the parent molecule (full-length zinc charged fetuin) in inducing apoptosis.

Abstract: The present invention provides polypeptides that include an O-linked glycosylation site that is not present in the wild-type peptide. The polypeptides of the invention include glycoconjugates in which a species such as a water-soluble polymer, a therapeutic agent of a biomolecule is covalently linked through an intact O-linked glycosyl residue to the polypeptide. Also provided are methods of making the peptides of the invention and methods, pharmaceutical compositions containing the peptides and methods of treating, ameliorating or preventing diseased in mammals by administering an amount of a peptide of the invention sufficient to achieve the desired response.

Abstract: A method of improving specific immune responses to small immunogens, haptens, has been developed by changing the linkage between the hapten and carrier being used for immunization. Antibodies to a glycated protein have been developed, utilizing an immunogen which is composed of a glycated peptide mimic of the glycated peptide sequence which is the target epitope, wherein the peptide mimic is constructed to conformationally mimic the conformation of the peptide in the native protein, the peptide mimic contains no charged groups or other immunodominant group, and the peptide mimic is connected to a spacer sequence equivalent to a peptide spacer of between one and thirty amino acids in length, which serves to position the peptide epitope in a conformation that approximates its conformation in the native protein. In a further embodiment the peptide mimic and spacer are linked to a carrier molecule.

Abstract: The invention provides non-affinity based isotope tagged peptides, chemistries for making these peptides, and methods for using these peptides. In one aspect, tags comprise a reactive site (RS) for reacting with a molecule on a protein to form a stable association with the peptide (e.g., a covalent bond) and an anchoring site (AS) group for reversibly or removably anchoring the tag to a solid phase such as a resin support. Anchoring may be direct or indirect (e.g., through a linker molecule). Preferably, the anchoring site comprises a biotin compound. Preferably, the tag comprises a mass-altering label, such as a stable isotope, such that association of the tag with the peptide can be monitored by mass spectrometry. The reagents can be used for rapid and quantitative analysis of proteins or protein function in mixtures of proteins.

Abstract: The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide having an isoleucine residue, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by an enzyme associated with the target cell. Methods of making and using the compounds are also disclosed.

Abstract: Specific detection of proteolytic enzymes is achieved by extinguishing dye fluorescence by the amino acid tryptophan. Ttyptophan is disposed on one side of the cutting site of a proteolytic enzyme while an amino acid marked with a dye is arranged on the other side. Extinction of fluorescence occurs prior to enzyme cutting. Spatial separation of the tryptophan and the dye takes place after cutting, whereby fluorescence extinction does not occur. The dye can then fluoresce and a signal increase occurs thereby indicating that cutting has been carried out and the presence of the enzyme.

Abstract: The invention relates to an isolated, synthetic or recombinant ?-conotoxin peptide having the ability to inhibit a neuronal amine transporter, nucleic acid molecules encoding all or part of such peptides, antibodies to such peptides and uses and methods of treatment involving them.

Abstract: Methods and reagents for site-selective functionalization of peptides and proteins. The methods most generally involve the reaction of a thioester with hydrazine. Reagents include bifunctional reagents of formula: H2N—NH—CH2-M-L-FG and salts thereof where M is a single bond or a chemical group carrying a non-bonding electron pair, such as —C(O)NR?—, where R? is H, or an alkyl or aryl group; L is an optional linker group as described above; and FG is a functional group having reactivity that is orthongonal to that of the hydrazine group. FG can, among others, be an azide, alkenyl, alkynyl, nitrile (—CN) or triazole group and is preferably an azide group (—N3). Methods and reagents can, for example, be combined with intein-mediated protein splicing to link proteins or fragments thereof to various chemical species or to a surface.

Abstract: A method is described for the site-specific preparation of hGRF-PEG conjugates containing one or more PEG units (per mole of hGRF) covalently bound to Lys12 and/or Lys21 and/or N?, characterized in that the conjugation reaction between the hGRF peptide and activated PEG is carried out in solution and the desired hGRF-PEG conjugate can be purified by chromatography. The conjugates prepared by this method, as well as their use in the treatment, prevention of diagnosis of growth hormone deficiency, are also an object of the present invention.

Abstract: The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the CD10 enzyme. Methods of treatment using the prodrug and methods of designing a prodrug are also disclosed.

Abstract: The present invention relates to cytostatics which have a tumor-specific action as a result of linkage to ?v?3 integrin antagonists via preferred linking units which can be selectively cleaved by elastase, i.e. by an enzyme which can especially be found in tumor tissue. The preferred linking units provide sufficient stability of the conjugate of cytostatic and ?v?3 integrin antagonist in biological fluids and, at the same time, the desired intracellular action within tumor cells as a result of its specific enzymatic or hydrolytic cleavability with release of the cytostatic.

Abstract: Cyclic homodetic peptides having a repeating D-L-chirality motif are shown to have a stable disk conformation with the amino acid side chains extending radially outward and the carbonyl and amino groups extending axially upward or downward. Such cyclic peptides can be employed as subunits in the assembly of molecular tubes. Cyclic peptides having a repeating D-L-chirality motif and lacking mutually repulsive side-chains are shown to stack atop one another in an anti-parallel fashion and are shown to be held together by the formation of ?-sheet hydrogen bonding. The stacked cyclic peptides form a molecular tube having a central channel. The diameter of the channel is determined by the size cyclic peptide. If the cyclic peptide includes ionizable amino acid residues, e.g. glutamic acid or lysine, assembly and disassembly of the molecular tubes can be controlled by varying the pH. If the cyclic peptide includes hydrophobic amino acid residues, the molecular tube will insert into a lipid membrane.

Abstract: Peptides have been identified that bind with high affinity to body surfaces, such as, hair, skin, nails, teeth, gums, and oral cavity surfaces. Diblock and triblock peptide-based body surface coloring reagents formed by coupling a body surface binding peptide to a pigment binding peptide, either directly or through a spacer, are described. The peptide-based body surface coloring reagents may be used in conjunction with pigments to color body surfaces.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group a peptide.

Abstract: The present invention provides a method for acylating one or more amino groups of a peptide where the acylation reaction is to be performed in an aqueous mixture containing less than 10% w/w aprotic polar solvent.

Abstract: A GPR7 ligand containing the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO:1 wherein the N-terminal amino acid residue may optionally be brominated, is useful in developing a receptor-binding assay system with the use of the GPR7 expression system, in screening a candidate compound for a drug such as an antiobestic, etc.

Abstract: Novel oligonucleotides comprising a sequence derived by a computer program are provided for inhibiting cytotoxic activity of lymphocytic cells, inhibiting production of inflammatory cytokines and inflammatory responses associated with those cytokines, inhibiting the activity of heme-containing enzymes and delaying the onset of an autoimmune disease. By combining the subject compositions with mixtures of cells comprising lymphocytic cells and cells which would otherwise activate the lymphocytic cells, lysis of the target cells can be substantially inhibited. The oligopeptides may be joined to a variety of other groups or compounds for varying the activity of the subject composition. The subject compositions may be administered by any convenient means to inhibit lymphocytic attack on tissue, particularly involved with xenogeneic or allogeneic transplants or to inhibit the production of inflammatory cytokines and inflammatory responses associated therewith.

Abstract: Methods for preparing viral neuraminidase inhibitors including antiviral peptides by specifically chemically modifying disulfide bonds in precursor molecules. A method of inhibiting viral neuraminidases by administering a viral neuraminidase inhibitor comprising an antiviral peptide prepared by the above methods and inhibiting the viral neuraminidase. Therapeutics for inhibiting viral neuraminidases, including effective amounts of viral neuraminidase inhibitors including antiviral peptides derived from selectively chemically modified disulfide bonds in precursor molecules, and present in a pharmaceutically acceptable carriers.

Abstract: The present invention is a method for a covalent ligation of one or more molecules to one or more surfaces, that is site-specific and both rapid and high yielding. The covalent ligation to the surface is based on the reaction of an azide and a phosphinothioester to form an amide bond. The method of the invention is particularly well-suited to the immobilization of peptides, proteins or protein fragments to surfaces.

Abstract: The present invention provides a process for preparing a peptide of formula I): Sub-[L]-[N(R1)-A-C(O)]p—[NH-A-C(O)]n+m—OH??(I) comprising: (a) reacting an immobilized compound of formula (II): Sub-(L)-[N(R1)-A-C(O)]p—[NH-A-C(O)]n—OH??(II) with an amino acid ester or peptide derivative of formula (III): H—[NH-A-C(O)]m—O(tBu)??(III) in the presence of a coupling agent to yield a peptide compound of general formula (IV): Sub-[L]-[N(R1)-A-C(O)]p—[NH-A-C(O)]n+m—O(tBu);??(IV) (b) removing the tBu (t-butyl) group to produce a solid-support bound carboxylic acid or peptide derivative of general formula (I); wherein n is a positive integer, e.g., 1–10, preferably 1–5; m is a positive integer, and P is 0–1.

Abstract: The present invention provides novel human glucagon-like peptide-1 (GLP-1) peptide mimics that mimic the biological activity of the native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. Further, the present invention provides novel, chemically modified peptides that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 mimics exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration.

Abstract: The present invention provides novel human glucagon-like peptide-1 (GLP-1) peptide mimics that mimic the biological activity of the native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. Further, the present invention provides novel, chemically modified peptides that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 mimics exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration.

Abstract: The present invention relates to a pharmaceutical composition comprising a GLP-1 derivative having a lipophilic substituent; and a surfactant.

Abstract: The invention relates to tissue inhibitor of metalloproteinase-2 (TIMP-2) as an osteoanabolically active peptide for use as a medicament for treating bone defects, bone diseases and for improving bone regeneration.

Abstract: The present invention relates to novel derivatives of exendin-4 or exendin-4 fragments, wherein the derivatives have a lipophilic substituent attached, optionally via a spacer, to an amino acid residue, which is not the N-terminal or C-terminal amino acid residue of the derivative.

Abstract: Peptides have been identified that bind with high affinity to hair, skin, and nails. Peptide-based hair conditioners, hair colorants, skin conditioners, skin colorants, and nail colorants are described. The peptide-based hair conditioners and hair colorants consist of a hair-binding peptide coupled to a hair conditioning agent or a coloring agent, respectively. The peptide-based skin conditioners and skin colorants consist of a skin-binding peptide coupled to a skin conditioning agent or a colorant, respectively. The peptide-based nail colorants consist of a nail-binding peptide coupled to a coloring agent. In all these compositions, the peptide may be directly coupled to the active agent or the coupling may be via a spacer. Personal care compositions containing these peptide-based conditioners and colorants are also described.

Abstract: Agents for blocking T cell-mediated immune reactions are provided. Such agents are peptides, referred to as “CD28 peptide mimetics”, of from 15 to 30 amino acids in length. The CD28 peptide mimetics comprise the hexapeptide motif ‘MYPPPY’, SEQ ID NO: 1, or a retro-inverso isomer thereof. The CD28 peptide mimetics further comprise flanking sequence at the amino and carboxyl terminus of the hexapeptide motif. Methods for treating subjects with T cell mediated autoimmune diseases or disorders are also provided. Such methods comprise administering one or more of the CD28 peptide mimetics to a subject with such a disease or disorder.

Abstract: The present invention relates to methods and compositions containing novel leptin peptides, preferably for the modulation of body mass (i.e., weight), more specifically for novel diagnostic and therapeutic applications in homeostasis of body weight and adipose tissue mass.

Abstract: Peptides having the following amino acid sequence as well as peptides or proteins which contain this amino acid sequence: R1-X01-X02-X03-X04-X05-X06-X07-X08-X09-X10-X11-X12-X13-R2. These peptides have a high affinity for immunoglobulins. Applications of the peptides according to the invention are also described.

Abstract: The present invention relates to compounds and methods for synthesizing compounds wherein the compounds exhibit extended circulating half-life in the blood. The increase in circulating half-life is achieved by conjugating polypeptides to binding groups that exhibit high affinity for human serum albumin.

Abstract: A dipeptide or tripeptide carrier system for active agent delivery to cells has an N-terminus natural amino acid and an active agent covalently bonded to a side chain of one of the remaining amino acid bases. The system is amenable to formulation as an oral administrant. The active agent being a therapeutic, a fluorescent dye, or contrast agent where the active agent has a molecular weight of less than 500 atomic mass units. An optional linker is provided intermediate between the active agent and the linking side chain.

Abstract: The present invention relates to conjugates of a lipid, substrate peptide of an enzyme secreted from the cells of mammals, including humans, and a water-soluble polymer that can be used as colloidal carriers and the like of tissue-specific drug delivery systems, methods of producing these conjugates, peptide-water-soluble polymer conjugates optionally having protective groups that are useful as the intermediates of these conjugates, colloidal carriers made from these conjugates, and tissue-specific drug delivery systems that use these colloidal carriers.

Abstract: Methods and compositions are provided for identifying compounds having affinity or complementarity to a target molecule. Compounds according to the invention may be described by the formula E-Ca—R—Cb-A, wherein E is a therapeutic or diagnostic agent, R is a reactive group, Ca and Cb are connector groups between E and R and between R and A, respectively, and A is an affinity group comprising the sequence F-1-Y-E-E. Compounds according to the invention may be used for labeling the target molecule, particularly where the target molecule is naturally found in a complex mixture, such as a physiological fluid, like blood. By affinity labeling in vivo, the lifetime of physiologically active entities can be greatly enhanced by becoming bound to long-lived blood components. The covalently bound entity may also serve as an antagonist or agonist of a particular binding protein or as an enzyme inhibitor.

Abstract: The present invention relates to compositions comprising thyroxine (T4) and triiodothyronine (T3). More specifically, the invention relates to thyroxine (T4) and triiodothyronine (T3) compositions that include a peptide carrier and thyroxine (T4) and triiodothyronine (T3) covalently attached to at least one of the N-terminus, the C-terminus, a side chain of the peptide carrier, and/or interspersed within the peptide chain; methods for protecting and administering thyroxine (T4) and triiodothyronine (T3); and methods for treating thyroid disorders.

Abstract: The present invention relates to cell adhesion promoting (“CAP”) peptide combinations that promote cell attachment or cell adhesion to culture surfaces that are otherwise cell adhesion resistant “CAR”. The invention provides combination of peptides that, when covalently coupled to a CAR layer such as hyaluronic acid that has been created on a polystyrene surface, promote cell attachment, growth differentiation, and execution of other desired cellular functions in culture.

Abstract: Fumaric acid amides of the general formula (I) wherein R1 represents OR3 or a D- or L-amino acid radical —NH—CHR4—COOH bonded via an amide bond, wherein R3 is hydrogen, a straight-chained or branched, optionally substituted C1-24 alkyl radical, a phenyl radical or C6-10 aralkyl radical and R4 is a side chain of a natural or synthetic amino acid and R2 represents a D- or L-amino acid radical —NH—CHR5—COOH bonded via an amide bond or a peptide radical comprising 2 to 100 amino acids bonded via an amide bond, wherein R5 is a side chain of a natural or synthetic amino acid, are used for preparing a drug (1) for the therapy of an autoimmune disease; (2) for use in transplantation medicine; (3) for the therapy of mitochondrial diseases; or (4) for the therapy of NF-kappaB mediated diseases.

Abstract: A solid phase synthesis method for preparing peptide-spacer-lipid conjugates, the peptide-spacer-lipid conjugates synthesized by the method, and liposomes containing the peptide-spacer-lipid conjugates. The present invention provides a convenient solid phase synthesis method for preparing peptide-spacer-lipid conjugates and provides various linkage groups (such as amide group) for conjugating peptide, spacer and lipid, wherein the spacer may comprise PEG. Several advantages can be achieved, such as the synthetic procedure can be simplified, the synthesis process can be set to automation, the purification is easier in each reaction step, and the product losses can be reduced to minimal during synthesis.

Abstract: We disclose haptotactic peptides having sequences homologous to specific portions of the carboxy terminal sequence of fibrinogen chains. The peptides derived from fibrinogen pre-C? chain possess activities of cell attraction or cell attachment to a surface to which the peptide is covalently bound.

Abstract: Methods are described for conjugating radioiodinated peptides or carbohydrate structures to proteins with improved yields and qualities of conjugates. In one method, specially designed radioiodinated bifunctional peptides containing nonmetabolizable amide bonds are coupled to antibodies. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to antibodies. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to antibodies. In a fourth method, a hydrazide-appended antibody is coupled to a radioiodinated carbohydrate or a thiolated antibody is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated antibody. Radioiodinated residualizing antibody conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group a peptide.

Abstract: A process for purification which permits satisfactory removal of impurities from a block copolymer consisting essentially of polyethylene glycols and poly(acidic amino acid) and is suitable for the production of a polymeric carrier having a pharmaceutically acceptable purity; a process for producing such a polymeric carrier; a block copolymer reduced in impurity content; a polymeric carrier as described above; pharmaceutical preparations in polymeric form, produced by the use of the carrier; and a method of subjecting polyethylene glycols and poly(acidic amino acids)—which are impurities contained in the block copolymer—to treatment with either an ion-exchange resin or a partition/absorption resin and then determining the quantities of them with a gel filtration column.

Abstract: The present invention relates to the protected intermediates and the deprotected products of P6A, related to the protected pseudopeptides introducing the protected intermediateds of P6A to 3S-(2-Boc)-1,2,3,4-tetrahydro-?-carboline-3-carboxylic acid and the deprotected pseudopeptides, related to the protected pseudopeptides introducing the protected intermediateds of P6A to 3S-1,2,3,4-tetrahydro-?-carboline-3-carboxylic acid benzyl ester, related to the methods for their preparation, and related to their use as the thrombolytic agents.