Abstract: This invention relates to a method of inverse solid phase synthesis in which reactants are reacted in solution and a solid phase matrix is used to separate unreacted reactants from desired product.

Abstract: A process is disclosed for the manufacture of amides, including peptides, in which a carboxylic acid is reacted with a primary or secondary amine in the presence of a carbodiimide and a catalytic amount of N-hydroxy compound.

Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.

Abstract: The invention is directed to a novel compound of formula ##STR1## in which R is a hydroxyl, alkyloxy, phenylalkyloxy or --NH--CH.sub.2 --COOH radical, R' and R" are identical and are each a hydroxy or methoxy radical and R'" represents a hydrogen, bromine, chlorine or iodine atom or a nitro radical. The invention is also directed to the salts of said compounds and their use.

Abstract: The invention relates to serine protease variants derived from precursor serine proteases via recombinant and/or chemical methods to form protease variants having improved peptide ligase activity. The invention also includes novel ligation substrates which in combination with the serine protease variants and a second ligation substrate are capable of forming a ligation product. The invention also relates to methods for forming such ligation products and the products formed thereby.

Abstract: Compounds of the formula I as well as methods for their preparation, their pharmaceutical preparations and their use. ##STR1## The compounds of formula I are useful in therapy, especially as analgesics and as immunosuppresive agents.

Abstract: A process for preparing and purifying cyclic peptides having disulfide moieties in a single processing operation which simplifies synthesis and reduces production costs, yet produces high, quality yield. Higher yields are obtained by isolating the desired cyclic compound through direct ion exchange chromatography as an integral part of the single process. The improved process is particularly useful for the preparation of vasopressin and oxytocin and their respective derivatives and analogs.

Abstract: Biologically active, backbone-cyclized peptides of the formula: ##STR1## wherein ?AA! or ?A.sup.1 A.sup.1 ! is a naturally occurring or synthetic amino acid residue, n or e is an integer of 1-10, m or d is 0 or an integer of 1-10, R is a naturally occurring or synthetic amino acid side-chain, E is a hydroxyl moiety or a carboxyl protecting group of a blocking group, optionally covalently attached to an insoluble polymeric support, and the circled line designates a spacer group of ##STR2## for formula I wherein M is --S--S--, --CO--NH-- or --S-- and p and q each is an integer of 2-10, or--(CH.sub.2).sub.p --(M).sub.x --Y (IV)for formula II wherein M is an amino or carboxyl group or a sulfur atom, p is an integer of 2-10, x is 0 or 1 and Y is a side-chain of a backbone amino acid. Also, processes for the preparation of these peptides and pharmaceutical compositions containing them.

Abstract: The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: ##STR1## or the acid fluoride salts thereof wherein BLK is an N-amino protecting groupAA is an amino acid residue andX is H or a protecting group useful,and the first amino and peptide have a free amino group and a blocked carboxy end.

Abstract: A process is disclosed for making peptides soluble in a water-immiscible organic solvent, comprising linking a lipophilic group with an amide or ester bond to the terminal carboxyl group of said peptide; when the lipophilic group is linked to L-serine, a molecule is obtained with a solubility in water at 25.degree. C. of less than 30 g/liter. This lipophilic group is non-polymeric and chemically defined. A process is also disclosed for the synthesis of peptides, optionally protected, in a liquid medium, wherein the starting material is an amino acid or peptide made soluble in an organic medium by a lipophilic group A--L linked to the carboxyl function of the starting amino acid or peptide, and are added to amino acids or peptides to be condensed which are activated on their acid function and protected on their amine function and are optionally protected on their side chain.

Abstract: A method is provided for preparing decapeptide and undecapeptide derivatives of LHRH by solution phase peptide chemistry as well as intermediate peptides useful in the same method.

Abstract: A method is provided for preparing decapeptide and undecapeptide derivatives of LHRH by solution phase peptide chemistry as well as intermediate peptides useful in the same method.

Abstract: Method and apparatus for synthesizing biopolymers, such as polypeptides and polynucleotides. The apparatus includes plural reaction vessels in which subunit coupling to biopolymers in a particle suspension is carried out. The vessels are connected to common valving structure for use in mixing the suspension and removing suspension liquid. In one embodiment, a robotic arm in the apparatus is operable to transfer reaction solution to the reaction vessels, and to transfer particle suspensions from the reaction vessels to a mixing vessel and back to the reaction vessels. The method can be used to produce preferably equi-molar amounts of different-sequence biopolymers, such as polypeptides and polynucleotides.

Abstract: N-Acyl-S-(2-hydroxyalkyl)cysteines, their preparation and their use as intermediates for the preparation of synthetic immunoadjuvants and synthetic vaccines.Compounds of the formula I ##STR1## in which the substances X, Y, R, R.sup.1 and R.sup.2 have the meanings mentioned, are suitable for the preparation of lipopeptides and lipoamino acids.

Abstract: A process of synthesizing a peptide using an alkylene oxide as an acid scavenger is provided. A process of the present invention can be used in a solid phase or solution phase synthetic process where peptide synthesis occurs by the sequential addition of N-.alpha.-amino-Boc-protected residues followed by acid deprotection of that N-.alpha.-amino protecting group and scavenging of the acid.

Abstract: This invention relates to a process for forming an amide or an ester from a reaction between an amine or an alcohol, respectively and an acylating derivative of a carboxylic acid, in the presence of an effective amount of a compound having the formula: ##STR1## and N-oxides thereof and salts thereof.

Abstract: Described is a peptide fragment which comprises the amino acid sequence 95-126 of ANF/CDD 1-126 (gamma-hANaP) and is formed in the kidney. The fragment urodilatin (ANF/CDD 95-126) has the following amino acid sequence: ##STR1## wherein R.sup.1 and R.sup.2 each represent further peptide fragments of ANF/CDD 1-126 (gamma-hANaP). In the amino acid sequence R.sup.1 is Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser and R.sup.2 is Asn-Ser-Phe-Arg-Tyr. Further described are processes for the preparation and/or recovery of the new peptide fragment and a medicament containing urodilatin (ANF/CDD 95-126) as well as medical indications of the medicament.

Abstract: New polypeptides comprising 32 amino acids, process for preparation thereof, application thereof as drugs and pharmaceutical preparations containing, as active ingredient, one or a plurality of said polypeptides. These polypeptides are used as active principles for new drugs, particularly indicated for osteoporoses of various origins.

Abstract: This invention relates to a process for forming an amide or an ester from a reaction between an amine or an alcohol, respectively and an acylating derivative of a carboxylic acid, in the presence of an effective amount of a compound having the formula: ##STR1## and N-oxides thereof and salts thereof.

Abstract: A process for producing peptide derivatives of formula (1) or salts thereof: ##STR1## which comprises condensation of peptide derivative of formula (2): ##STR2## with carboxylic acid of formula (3): ##STR3## or condensation of a peptide derivative of formula (4): ##STR4## with a protected amino acid of formula (5'): ##STR5## wherein R.sup.1 and R.sup.2 are a lower alkyl group or hydrogen atom, R.sup.3 is a lower alkyl group, X is a methylthiomethyl, methanesulfonylmethyl, carbamoylmethyl, or a lower alkyl group, Ar is an aryl or heteroaryl group, and A.sup.4 is Ar--O--CH.sub.2 --CO. The peptide derivatives and salts thereof are useful as the human immunodeficiency virus (HIV) protease inhibitors.

Abstract: A process is provided for the total synthesis of a cyclic peptide, which is useful as antifungal drug, and novel compounds prepared by the synthesis method. The cyclic peptide is represented by the following formula (I): ##STR1## wherein X1, X2, X4 and X7 are independently N-methyl-.alpha.-amino acid or .alpha.-hydroxy acid,provided that at least one of X1, X2, X4 and X7 is an .alpha.-hydroxy acid;X3, X6 and X8 are independently .alpha.-amino acid;X5 is a cyclic amino acid;X9 is an N-methyl-.alpha.-amino acid or .alpha.-hydroxy acid substituted by a hydroxy group;and the dotted lines represent intramolecular hydrogen bonds.The process includes cyclizing a corresponding linear peptide between X5 and X6 via a peptide bond.

Abstract: There is disclosed single chain peptide compounds, substituted at a C.alpha.-atom of a non-terminal amino acid by a group--A which is defined in claim 1. The native .alpha.-side chain of the C.alpha. atom bonded group to group --A absent. The peptide derivatives according to the invention are useful for inhibiting cell proliferation, especially myelopoietic and bone marrow cells.

Abstract: A solid phase coupling reagent for amide formation, comprising insoluble polymer bearing pendant side chains, said side chains each comprising a terminal portion having the formula ##STR1## wherein Y.sup.- is a counteranion and n is independently an integer from 2 to 6; and a method of making amides employing the coupling reagent.

Abstract: The invention relates to a reagent which is useful for cleaving an alkoxycarbonyl group from a functional group which it is protecting and to a process for using this reagent. This reagent comprises a phenol, a diluent, and a hydrohalic or hydropseudohalic acid, the acidity of which is at least equal to that of formic acid. The method is advantageously applied in the synthesis of peptides.

Abstract: A process for preparing and purifying cyclic peptides having disulfide moieties in a single processing operation which simplifies synthesis and reduces production costs, yet produces high, quality yield. Higher yields are obtained by isolating the desired cyclic compound through direct ion exchange chromatography as an integral part of the single process. The improved process is particularly useful for the preparation of vasopressin and oxytocin and their respective derivatives and analogs.

Abstract: New sub-monomer synthetic methods for the preparation of peptide nucleic acid oligomeric structures are disclosed that provide for the synthesis of both predefined sequence peptide nucleic acid oligomers as well as random sequence peptide nucleic acid oligomers. Further these methods also provide for the incorporation of peptide nucleic acid units or strings of such units with amino acids or strings of amino acids in chimeric peptide nucleic acid-amino acid compounds. Further disclosed are method of making random libraries of peptide nucleic acids using the fully preformed monomers.

Abstract: A process for the manufacture of amides, including peptides, by reacting a carboxylic acid with a primary or secondary amine in the presence of a carbodiimide and a catalytic amount of a N-hydroxy compound.

Abstract: Process for the diastereoselective reductive pinacol coupling of homochiral .alpha.-aminoaldehydesA process for the preparation of optically pure symmetrical compounds of the formula I ##STR1## is described, in which R.sup.1, R.sup.2 and R.sup.3, are explained in the description, with simultaneous control of the four centers of chirality indicated by *.

Abstract: A peptide of the following general formula is subjected to cyclization reaction to produce a cyclic peptide, preferably a synthetic calcitonin derivative (elcatonin) which is a useful medicine. ##STR1## (wherein A and B form a peptide of the formula Ser-Asn-Leu-Ser-Thr (SEQ ID NO: 43); X means a hydroxyl group, a carboxy-protecting group, an amino acid residue or a peptide residue; provided that the side-chain carboxyl group of .alpha.-L-aminosuberic acid is condensed with an amino acid or a peptide). The cyclic peptide can be obtained by subjecting a peptide of the above general formula to (1) cyclization reaction by chemical condensation, (2) cyclization reaction in the presence of an alkali metal salt and (3) reactions using the techniques of liquid phase synthesis and solid phase synthesis in combination.

Abstract: The present invention is drawn to a process for forming an amide bond linkage comprising reacting a carboxylic acid and an amine in a two-phase mixture of water and an organic solvent selected from an oxygenated organic solvent or an aromatic solvent in the presence of a coupling reagent and an additive. This process is useful for making ubiquitous amides and polypeptides having various biological activities.

Abstract: A method for synthesizing polypeptides from amino acids and/or peptides utilizing a novel reaction medium containing a hydrated silica entity containing silanol groups which function as an inorganic enzyme.

Abstract: The invention concerns novel renin-inhibitory compounds which contain an amino-substituted heterocycle at the P.sub.2 position. These are useful for treating renin-associated hypertension, congestive heart failure, glaucoma, hyperaldosteronism, and diseases caused by retroviruses including HTLV-I and -III. Processes for preparing the compounds, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, or hyperaldosteronism.

Abstract: In this invention, a peptide of the following general formula is subjected to cyclization reaction to produce a cyclic peptide, preferably a synthetic calcitonin derivative (elcatonin) which is a useful medicine. ##STR1## (wherein A and B form a peptide of the formula Ser-Asn-Leu-Ser-Thr (SEQ ID NO: 47); X means a hydroxyl group, a carboxy-protecting group, an amino acid residue or a peptide residue; provided that the side-chain carboxyl group of .alpha.-L-aminosuberic acid is condensed with an amino acid or a peptide).The cyclic peptide can be obtained by subjecting a peptide of the above general formula to (1) cyclization reaction by chemical condensation, (2) cyclization reaction in the presence of an alkali metal salt and (3) reactions using the techniques of liquid phase synthesis and solid phase synthesis in combination.

Abstract: Processes for synthesizing polypeptides containing substantially non-antigenic polymers, preferably poly(alkylene glycols) in specifically predetermined sites are disclosed. Polypeptides prepared by such processes acre also disclosed.

Abstract: A solid phase coupling reagent for amide formation, comprising insoluble polymer bearing pendant side chains, said side chains each comprising a terminal portion having the formula ##STR1## wherein Y.sup.- is a counteranion and n is independently an integer from 2 to 6; and a method of making amides employing the coupling reagent.

Abstract: A process and intermediates for the manufacture of S-3-methylheptanoic acid from S-citronellol; a novel crystalline form of immunoregulatory N-(S-3-methlylheptanoyl)-D-gamma-glutamyl-glycyl-D-alanine, an immunoregulatory agent; and an improved process and intermediates therefor.

Abstract: The invention allows the generation and screening of a large population of peptides for the presence of peptides which bind a particular macromolecule or macromolecular complex with high affinity, and further allows the favored net synthesis of analyzable quantities of such peptides, by using as the "trap" a macromolecule or macromolecular complex for which binding of the peptide is desired. The starting mixture is preferably spiked with a peptide having some affinity for the target macromolecule so that mutation of the spike or "lead" peptide is favored. The development of improved binding peptides through scrambling may be dynamically monitored by initially binding the target with an insolubilized ligand, and then looking for an increase in the concentration of the target in the soluble phase as a result of the displacement of the reference ligand by scrambled peptides.

Abstract: There are described a device and method for doing confined reactions such as PCR amplification and detection, wherein solids (e.g., beads) used to obtain separation between bound and "free" label reagents, are transferred from region to region, specifically through a wash liquid so as to wash off the "free" label reagent from the solids. Separate chambers have dividers that are overcome by piercing or by liquification, to create passageways for the transfer of the solids. The passageways remain contained within the device.

Abstract: Disclosed herein is purified isolated angiogenic factor, isolated from Live Yeast Cell Derivitive. Also disclosed herein are methods to treat mammals suffering from wounds or burns comprising administering the angiogenic factor and pharmaceutical formulations for use in the methods.

Abstract: A solution phase process for making peptides having biological activity or peptide intermediates which can be used to prepare peptides having biological activity is described. The process involves the condensation reaction of two peptide fragments.

Abstract: Protected and unprotected di- or oligopeptides are synthesized by reacting an N-terminally protected .alpha.-amino acid alkyl ester or peptide alkyl ester of the formula X--E--R.sup.1 with an amino acid or a di- or oligopeptide or a derivative thereof of the formula H.sub.2 N--Q--R.sup.2 in aqueous solution in the presence of a hydrolase, and, removing protective groups from the reaction product separated from the reaction mixture, where E is the residue of an .alpha.-amino acid or of a di- or oligopeptide, R.sup.1 is lower alkyl and X is a group which carries a charge or is polar at the pH values used for the reaction and which increases the solubility by a factor >5 compared with compounds wherein X=H, Q is the residue of an amino acid or of a di- or oligopeptide, and R.sup.2 is an optionally esterified or amidated acid group. In a preferred embodiment, the peptide or (.alpha.

Abstract: The invention concerns novel renin-inhibitory peptides which are useful for treating renin-associated hypertension, congestive heart failure, hyperaldosteronism and diseases caused by retroviruses including HTLV-I and -III. Processes for preparing the peptides, novel intermediates useful in the preparation thereof, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, congestive heart failure, or hyperaldosteronism.

Abstract: A method for monitoring the reaction between an activated carboxylic acid derivative and an amine, such as the formation of a peptide bond in peptide synthesis, whereby an inert anionic dye component and an inert cationic component are included in the reaction system, in small relative amounts compared to the carboxylic acid derivative. The distribution of the dye component to the cationic component, when separated from the amine component, is monitored and at a given maximum value indicates a substantially quantitative reaction.

Abstract: Chemical reactions are readily carried out using supercritical carbon dioxide as the reaction medium. Supercritical carbon dioxide is of special value as a reaction medium in reactions for synthesizing polypeptides, for sequencing polypeptides, or for amino acid analysis.

Abstract: Disclosed herein is purified isolated angiogenic factor, isolated from Live Yeast Cell Derivative. Also disclosed herein are methods to treat mammals suffering from wounds or burns comprising administering the angiogenic factor and pharmaceutical formulations for use in the methods.

Abstract: The preparation of small peptides with multiple disulfide bonds is accomplished by forming a prepropeptide with an N-terminal excised region separated from the cysteine-rich peptide by one or more cleavable amino acid residues. The excised region preferably consists of an N-terminal end providing a hydrophobic signal sequence domain having up to approximately 25 amino acids, and an intermediate central propeptide domain having a variable length of between about 5-50 amino acids. The N-terminal excised region serves as a folding template to direct the formation of specific disulfide bonds in the cysteine-rich peptide. The cysteine-rich peptide is cleaved by enzymes releasing the biologically active peptide.

Abstract: A stabilized complex comprising a growth hormone and an aromatic aldehyde. Specifically, the complex comprises porcine somatotropin and a substituted benzaldehyde and to a method of providing a prolonged release of the somatotropin and improved feed efficiency in animals.

Abstract: New polymer supports containing cleavable cross-links are described which are suitable for solid phase peptide synthesis and can then be solublized for further chemical or biological manipulation (including immunization) in solution.

Abstract: The present invention relates to a process for preparing optically active synthons, in which an oxygen-silylated amino acid or peptide having a protected nitrogenous group, is activated by a non-coordinated halogenated phosphorus derivative and is condensed with an N-silyl amino acid or peptide in which the acid group is protected.

Abstract: A process and intermediates for the manufacture of S-3-methylheptanoic acid from S-citronellol; a novel crystalline form of immunoregulatory N-(S-3-methylheptanoyl)-D-gamma-glutamyl-glycyl-D-alanine, an immunoregulatory agent; and an improved process and intermediates therefor.