Abstract: Improved methods of native chemical ligation are provided. The methods involve reacting a thioacid (e.g. a peptide thioacid) with an aziridinyl compound (e.g. an aziridinyl peptide) under mild conditions without the use of protecting groups, and without requiring that a cysteine residue be present in the ligation product. Initial coupling of the thioacid and the aziridinyl compound yields a ligation product which contains an aziridinyl ring. Subsequent opening of the aziridinyl ring (e.g. via a nucleophilic attack) produces a linearized and modified ligation product.

Abstract: Methods for building peptide chains containing sulfonyl modified amines at the N-terminus, or, within amino acid side chains, of a growing peptide in a solid-phase peptide synthesis are described. Further, compositions having a sulfonyl modified amine attached to the N-terminus, or within an amino acid side chain, of a polypeptide containing three or more amino acid residues are described.

Abstract: The present invention concerns new thiolysine and selenolysine compounds that can be used as building blocks for peptides and proteins, providing ligation handles for site- and chemoselective modification of said peptides and proteins. In particular, the invention provides. In particular, the invention provides (the use of) the compounds 5-thiolysine (also referred to as ?-thiolysine); 4-thiolysine (also referred to as ?-thiolysine); 5-selenolysine (also referred to as ?-selenolysine) and 4-selenolysine (also referred to as ?-selenolysine). The positioning of the thiol or selenol group at the respective carbon atom allows for a very efficient intramolecular transfer reaction to take place after conjugation with a selected ligand, and the thiol or selenol group may subsequently be removed using reported procedures, thereby restoring the native lysine structure, or be used as an additional conjugation handle. The methodology is fast and gives well-defined material.

Abstract: The present invention relates to processes for preparing a polypeptide or pharmaceutically acceptable salt thereof comprising L-tyrosine, L-alanine, L-glutamate, and L-lysine. The polypeptide or pharmaceutically acceptable salt thereof is preferably glatiramer acetate.

Abstract: Methods for analyzing, selecting, characterizing or classifying compositions of a co-polymer, e.g., glatiramer acetate are described. The methods entail analysis of pyro-glutamate in the composition, and, in some methods, comparing the amount of pyro-glutamate present in a composition to a reference standard.

Abstract: The invention provides pharmaceutical compositions and method for inhibiting growth of prostatic adenocarcinoma, stomach cancer, breast cancer, endometrial, ovarian or other cancers of epithelial secretion, or benign prostate hyperplasia (BPH). In one embodiment the pharmaceutical composition includes human rHuPSP94, antigenic portions thereof, and functionally equivalent polypeptides thereof. In another embodiment, the pharmaceutical composition includes a mixture of human rHuPSP94, antigenic portions thereof, and functionally equivalent polypeptides thereof and an anticancer drug which may be administered in an appropriate dosage form, dosage quantity and dosage regimen to a patient suffering from, for example of prostatic adenocarcinoma, stomach cancer, breast cancer, endometrial, ovarian or other cancers of epithelial secretion, benign prostate hyperplasia, or (BPH) gastrointestinal cancer.

Abstract: The present invention relates to an improved process for preparing a polypeptide or pharmaceutically acceptable salt thereof comprising L-tyrosine, L-alanine, L-glutamate, and L-lysine. The polypeptide or pharmaceutically acceptable salt thereof is preferably glatiramer acetate.

Abstract: The present invention provides compositions and methods for protecting cells and tissues from damage associated with therapeutic treatments of cancers and other diseases and conditions where reactive oxygen species are produced. The present invention also provides compositions useful as research reagents.

Abstract: Methods for analyzing, selecting, characterizing or classifying compositions of a co-polymer, e.g., glatiramer acetate are described. The methods entail analysis of pyro-glutamate in the composition, and, in some methods, comparing the amount of pyro-glutamate present in a composition to a reference standard. In some cases, the methods entail treating the co-polymer with pyro-glutamate aminopeptidase to cleave N-terminal pyro-glutamate residues.

Abstract: A solid phase peptide synthesis method is disclosed. The method includes the steps of deprotecting an amino group in its protected form that is protected with a protecting group that includes an ?,?-unsaturated sulfone; washing the deprotected acid in a solvent selected from the group consisting of water, alcohol, and mixtures of water and alcohol; coupling the deprotected acid to a resin-based peptide or a resin-based amino acid; and washing the coupled composition in a solvent selected from the group consisting of water, alcohol, and mixtures of water and alcohol.

Abstract: The present invention concerns new thiolysine and selenolysine compounds that can be used as building blocks for peptides and proteins, providing ligation handles for site- and chemoselective modification of said peptides and proteins. In particular, the invention provides. In particular, the invention provides (the use of) the compounds 5-thiolysine (also referred to as ?-thiolysine); 4-thiolysine (also referred to as ?-thiolysine); 5-selenolysine (also referred to as ?-selenolysine) and 4-selenolysine (also referred to as ?-selenolysine). The positioning of the thiol or selenol group at the respective carbon atom allows for a very efficient intramolecular transfer reaction to take place after conjugation with a selected ligand, and the thiol or selenol group may subsequently be removed using reported procedures, thereby restoring the native lysine structure, or be used as an additional conjugation handle. The methodology is fast and gives well-defined material.

Abstract: Methods of making copolymers are described.

Abstract: An instrument and method for accelerating the solid phase synthesis of peptides are disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, activating a second amino acid, coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.

Abstract: A novel compound of formula I is devised.

Abstract: The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

Abstract: An instrument and process for accelerating the solid phase synthesis of peptides is disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, then activating a second amino acid by adding the second acid and an activating solution to the same vessel while irradiating the vessel with microwaves, then coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.

Abstract: The present invention relates to an improved process for the preparation of N6-(aminoiminomethyl)-N2-(3-mercapto-1-oxopropyl)-L-lysylglycyl-L-?-aspartyl-L-tryptophyl-L-prolyl-L-cysteinamide, cyclic(1?6)-disulfide of formula (1), which involves assembling a peptide chain comprising of six amino acids and a thioalkyl carboxylic acid in a required sequence on a solid support to obtain a peptide bound resin of formula (2), capping the free amino groups after each coupling, cleaving Dde group in the peptide of formula (2) from the solid support to obtain peptide-solid support of formula (3), guanylating the peptide of formula (3) at ?-lysine-NH2 in an organic solvent to obtain peptide-solid support of formula (4), cleaving and deprotecting all groups in the peptide of formula (4) from the solid support to obtain peptide-amide formula (5), oxidizing the SH-peptide of formula (5) with an appropriate oxidizing agent to obtain the crude peptide-amide of formula (1) and purifying the crude peptide-amide of formula (1)

Abstract: An azapeptide derivative of growth hormone releasing peptide (GHRP) of Formula I: A-(Xaa)a-N(RA)—N(RB)—C(O)-(Xaa?)b-B which binds to CD 36.

Abstract: The present invention provides for an efficient process for making Pramlinitide, as well as novel intermediates for the making of the same.

Abstract: The invention concerns a novel method for preparing an intermediate polyanion for preparing cyclosporin derivatives by treating a cyclosporin with a hexamethyldisilazane metal salt, optionally in the presence of a metal halide. The treated cyclosporin has one or several free hydroxy groups and/or non-methylated nitrogen atoms in position ? and/or any other acid group capable of deprotonation which are optionally deprotonated or in protected form.

Abstract: According to the present invention, there is provided a range of new conotoxin derivatives and methods for synthesizing these analogues and other intramolecular dicarba bridge-containing peptides, including dicarba-disulfide bridge-containing peptides.

Abstract: A method for synthesizing a given peptide or its derivative which contains a proline residue or a proline derivative, at proximity to, or at, the C-terminal end of said peptide is provided. The method comprises a) synthesizing on a first resin a C-terminal portion of said peptide, or its derivative, comprising at least three successive amino acid residues or their derivatives, by successive coupling of selected amino acids, small peptides or their derivatives; b) cleaving the C-terminal portion from said first resin; c) reattaching said C-terminal portion to a second resin which is generally suitable for the synthesis of peptides but is unsuitable for the formation of peptides having a proline residue positioned at the C-terminal end of said peptide; and d) coupling selected amino acids, small peptides or derivatives to the C-terminal portion.

Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

Abstract: A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.

Abstract: An instrument and method for accelerating the solid phase synthesis of peptides is disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, then activating a second amino acid by adding the second acid and an activating solution to the same vessel while irradiating the vessel with microwaves, then coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.

Abstract: A solution phase synthetic method for preparing basic tripeptides of the formula Gly-Xaa-Gly-X which have in various biological properties such as stimulating protein production when used as additives in a bioreactor. The basic tripeptides of the invention may be produced on gram or kilogram scale.

Abstract: An instrument and process for accelerating the solid phase synthesis of peptides is disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, then activating a second amino acid by adding the second acid and an activating solution to the same vessel while irradiating the vessel with microwaves, then coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.

Abstract: The subject invention provides an improved process for obtaining a mixture of polypeptides having nonuniform amino acid sequences, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and lysine where the resulting mixture of polypeptides comprises less than 0.3% brominated tyrosine and less than 1000 ppm metal ion impurities.

Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.

Abstract: Method of making metallopeptides is provided, for use in biological, pharmaceutical and related applications. The metallopeptides are made of peptides, peptidomimetics and peptide-like constructs, and include a metal ion-binding region thereof which includes at least one orthogonal sulfur-protecting group, in which the peptide, peptidomimetic or construct is conformationally fixed on deprotection of the sulfur and complexation of the metal ion-binding region with a metal ion while the peptide, peptidomimetic or construct is cleavably bound to solid phase.

Abstract: A novel method for side chain cyclisation of peptides by means of lactamization is provided.

Abstract: An instrument and process for accelerating the solid phase synthesis of peptides is disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, then activating a second amino acid by adding the second acid and an activating solution to the same vessel while irradiating the vessel with microwaves, then coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.

Abstract: The invention relates to conjugates comprising all or part of the amino acid sequences of at least one peptide derived from an extracellular loop of the P-170 protein. The peptide may be covalently attached to spacers which may be polyethyleneglycol (PEG), polyglycine, polylysine or any polymer chain suitable for human use and is coupled at its free end to a phospholipids, e.g., phosphatidylethanolamine or any other chemically suitable phospholipid.

Abstract: Methods and protected amino acids useful as building blocks (protected monomers) for the synthesis of peptides and proteins that are selectively modified at one or more side-chain hydroxyl groups. Azide-bearing protecting groups allow the selective deprotection of side-chain hydroxyl groups of amino acids after synthesis of a peptide. Reaction conditions for removal of the azide-bearing protecting group can be selected which are substantially orthogonal to those that will remove ?-amino protecting groups typically employed in peptide synthesis, such that hydroxyl groups protected with the azide-bearing protecting group remain protected during synthesis of the peptide chain. Various protecting groups which are readily available can be used for protecting potentially reactive side chain groups of amino acids in the peptide or protein to be modified.

Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

Abstract: Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

Abstract: Synthetic methods and compounds involving amino amides, peptides and peptidomimetics. Amino amide derivatives are prepared via the one-step three-component reaction of a glyoxamide, an amine, and an organoboron derivative. Conversion of the product to another glyoxamide intermediate allows the iterative use of this chemistry for the synthesis of peptides and peptidomimetics.

Abstract: A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.

Abstract: The invention concerns a novel method for preparing an intermediate polyanion for preparing cyclosporin derivatives by treating a cyclosporin with a hexamethyldisilazane metal salt, optionally in the presence of a metal halide. The treated cyclosporin has one or several free hydroxy groups and/or non-methylated nitrogen atoms in position ? and/or any other acid group capable of deprotonation which are optionally deprotonated or in protected form.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: The present invention is a method for producing a peptide or a protein in which a side chain contains a modified amino acid residue, which comprises chemically producing a peptide fragment containing an amino acid residue having a modified side chain using an weak acid-cleavable resin, producing a peptide fragment containing no amino acid residue having a modified side chain using a genetic recombination method or/and an enzymatic method, and condensing the resulting two kinds of peptide fragments and, according to the present invention, a peptide or a protein containing modification such as acylation, glycosylation and phosphorylation can be obtained effectively and at high quality.

Abstract: A method of perlecan isolation (from the EHS tumor) which produces “clean” (i.e. substantially “pure”) perlecan is disclosed. Clean perlecan is thus produced in sufficient quantities for use in a number of different in vitro and in vivo assays. In addition, this isolation method exploits a newly discovered aggregating property of a ˜220 kDa heparan sulfate proteoglycan (HSPG) observed during gel filtration chromatography, which allows it to be effectively separated from non-aggregating perlecan. The method employs specific cation exchange, anion exchange, molecular sieve chromatography and immobilized GAG affinity chromatography. It is demonstrated that there are no other contaminating proteins in the perlecan and HSPG preparations, and that the perlecan core protein is intact. Improved, clean perlecan based, rodent models of fibrillar amyloid protein deposition, accumulation and/or persistence in tissues are disclosed.

Abstract: A process for the preparation of a polypeptide designated in the present invention as 1, composed of the following amino acid units in the structure, namely: L-alanine, L-glutamic acid, L-lysine and L-tyrosine randomly arranged in the polypeptide 1, or pharmaceutically acceptable salts thereof, comprising the steps of: (a) polymerization of a mixture of the N-carboxyanhydrides of L-alanine, L-tyrosine, a protected L-glutamate and a protected L-lysine to obtain protected copolymer 6 or salt thereof; (b) deprotection of the protected copolymer 6 (or salt thereof) to produce polypeptide 1 or a pharmaceutically acceptable salt thereof in one single step; (c) separation and purification of the polypeptide 1 (or a pharmaceutically acceptable salt) to obtain a purified polypeptide 1

Abstract: Novel metal binding ligands are disclosed that may be coupled to peptides for use in methods of diagnosis and therapy. Peptides containing the ligands are produced using a method wherein ligand introduction or cyclization can be conducted at any point during the synthesis of the peptide. Such peptide derivatives are readily labeled with radiometals, such as isotopes of rhenium or technetium, while retaining their ability to tightly bind specific peptide receptors.

Abstract: An process for the reversible modification of membrane interaction of a compound is described. Modification of membrane interaction can be used to facilitate delivery of molecules to cells in vitro and in vivo. The described modifiers, which are used to reversibly inactivate the membrane active compounds, can also be utilized as cross-linkers or to reverse the charge of a molecule.

Abstract: A peptide factor, its analogs and methods of using such peptide factor derived from murine epidermal growth factor peptide is disclosed wherein the peptide factor is modified to protect it from proteolytic degradation and the peptide binds to laminin receptors.

Abstract: Synthetic methods and compounds involving amino amides, peptides and peptidomimetics. Amino amide derivatives are prepared via the one-step three-component reaction of a glyoxamide, an amine, and an organoboron derivative. Conversion of the product to another glyoxamide intermediate allows the iterative use of this chemistry for the synthesis of peptides and peptidomimetics.

Abstract: The invention provides apparatus and methods for determining the nucleotide sequence of target nucleic acids using hybridization to arrays of oligonucleotides. The invention further provides apparatus and methods for identifying the amino acid sequence of peptides that bind to biologically active macromolecules, by specifically binding biologically active macromolecules to arrays of peptides or peptide mimetics.

Abstract: The synthesis of peptides comprising disulphide bridges is challenging since it is difficult to ensure that the correct cysteine residues combine to form the desired disulphide bridges. The present invention describes novel protection techniques useful in the preparation of peptides. Described is a process for the deprotection of an Acm-, MBzl- and/or tBu-protected thiol which comprises reacting said protected thiol with an acid in the presence of an oxidising agent at a temperature sufficient to effect deprotection and generation of disulphide bonds.

Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.