Abstract: Trisubstituted N-protected guanidines and methods for use as guanidinylating reagents to yield N-protected guanidine derivatives.

Abstract: Disclosed is a synthetic method for the preparation of analogs of Didemnin A (1), particularly the Amino-Hip analog of Didemnin A, also known as “AipDidemnin A” (8).

Abstract: The invention relates to compounds of formula where R is a structural diversity element selected from the group consisting of alkyl, cycloalkyl, aryl, heteroaryl, peptidyl, heteroatom-substituted alkyl, cycloalkyl, and amines; and Nu is a structural diversity element derived from a nucleophile, NuH, selected from the group consisting of amines, amino acids, peptide, water, hydrogen sulfide, alcohols, and thiols. The invention also relates to arrays and combinatorial libraries of such compounds, and to a method of preparing such compounds.

Abstract: A procedure for obtaining the somatostatin analog, octreotide by means of solid phase synthesis on polymer supports and by intervention of protector groups of the Fmoc/tBu type. It includes construction of the seven amino acid, Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)Thr(tBu)-Cys(Trt)-Cl-trityl-R linear peptide, in which R is a polymer; treatment of the resulting peptidyl-resin with acid, for detachment of the peptide from the resin; cycling the linear structure obtained by reaction with iodine before or after incorporation of the threoninol residue into the terminal carboxy end; incorporating the threoninol residue in solution upon the seven amino acid protected peptide with or without the disulfide bridge formed; and removing the protections at the N-terminus and at the side chains with a treatment with 70-95% TFA in presence of scavengers to obtain octreotide.

Abstract: The present invention relates to a reaction and dissolving medium for the synthesis of peptides. This reaction and dissolving medium for peptide synthesis and/or purification comprises a diluent A chosen from a group of water-immiscible solvents and a phenol B. By employing this reaction and dissolving medium, peptides can be synthesized which are useful as medicaments, vaccines, agro-foodstuff products or plant protection products.

Abstract: The invention provides compounds and processes for synthesis of peptide nucleic acids (PNA). The compounds include temporary amino protecting groups that are base-labile, and protection groups for the exocyclic amino function of the nucleotide base that is compatible with the base-labile amino protecting group. Cleavage of an oligomer comprising these compounds from a solid support can be achieved using weak or medium strength acids.

Abstract: This invention relates to a novel process for the synthesis of vasoactive intestinal peptide analog Ac(1-31)-NH2 from four protected peptide fragments.

Abstract: Nucleic acid analogues provide a particularly useful tool for the preparation of complex polymeric structures of defined geometry because they are relatively stable to reaction conditions for the preparation of such structures and provide the opportunity to introduce reactive groups which would not be possible with usual nucleic acids. These supramolecular structures can be used to form fine networks in nanometer size, for the preparation of e.g., computer chips, new materials/polymers with conductivity and/or insulator properties, and robot arms in nanometer scale.

Abstract: Disclosed herein is a process whereby oligopeptides are ligated to form ligation peptide products. In the first step, two starting oligopeptides are ligated to form an intermediate having an amino-thioester linkage. In the second step, the aminothioester linkage undergoes a rearrangement to form a peptide having an N-substituted amide linkage. In an optional third step, the N-substitution of the amide linkage is chemically removed to form a native peptide linkage.

Abstract: The present invention relates to a class of pentapeptide analogs of LHRH. These compounds are useful in the treatment of disease conditions which are mediated by reproductive hormones, including benign prostate hyperplasia, prostate tumors, breast and ovaries tumors, cryptorchidism, hirsuitism, gastric motility disorders, dysmenorrhea, and endometriosis.

Abstract: A method is provided which facilitates and enables the production of a wide range of complex conjugates composed of similar or dissimilar units linked together by amide bonds. Said method for the production of acylthio derivatives, R′—CO—SA, involves reaction of a carboxylate, R′—CO—O− (or carboxylic acid R′—CO—OH) with an iso-thiouronium derivative (bearing SA) in the presence of base. Nucleophilic counterion forms of the iso-thiouronium salts confer significant rate enhancement. The processes are simple, generally applicable, efficient, and do not require the employment of noxious reagents. The production of complex protein-like products by the intermediary of acylthio esters generated by the process of this invention, provides a method which is compatible with mild methods of chain assembly; and is preferably applied when the second component in the ligation bears an amino terminal cysteine residue.

Abstract: This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides. The method lends itself to automation and is ideally suited for large scale manufacture of oligonucleotides with high efficiency.

Abstract: A method for preparing a peptide derivative of formula (I) or a salt thereof: which method comprises the steps of removing two MBzl groups from a compound of formula (II) or a salt thereof: wherein MBzl represents a 4-methoxybenzyl group which serves as a protective group for a thiol group, and R1 and R2 represent hydrogen or a protective group for Trp or Arg respectively; and subsequently oxidizing in an aqueous medium having a pH from 4 to 6 to form an intramolecular disulphide bond; intermediates useful for preparing the compounds of formula (I) and preparation of the intermediates.

Abstract: A process is disclosed for the esterification of an amino acid or peptide in which the amino acid or peptide is converted into the corresponding ester in the presence of a hydrosulphate have the general formula ROSO3H, where R represents an alkyl group, with the hydrosulphate being prepared, in the presence of the amino acid or peptide, from chlorosulphonic acid and an alcohol having the general formula ROH, where R has the same meaning as above. The chlorosulphonic acid to amino acid or peptide molar ratio preferably is between 0.8 and 2.0, in particular between 1.0 and 1.3. A primary alcohol, in particular methanol, is preferably used as alcohol. The amino acid used may be for example an &agr;-amino acid chosen from the group comprising p-hydroxyphenylglycine, phenylglycine, phenylalanine, tyrosine, proline and valine; L-alanyl-L-proline or an ester of L-aspartyl-L-phenylalanine, for example, may be used as peptide.

Abstract: Protease enzyme from Bacillus subtilis and Bacillus sp. Catalyzes the acylation of organic solvent-insoluble macromolecules in isooctane solution containing vinyl esters of fatty acids, lactones or lactides as acyl donors. The reaction occurs only when the enzyme is solubilized via ion-pairing with the anionic surfactant dioctylsulfosuccinate, sodium salt (AOT). Enzyme based acylation was demonstrated in macromolecules such as silk proteins. These macromolecules are reactive either as cryogenically milled powder suspended in the organic solvent or as a thin film deposited onto ZnSe slides. This selective acylation approach represents the first attempt at using enzymes to modify organic-insoluble macromolecules in nonaqueous media.

Abstract: The present invention relates to a process for forming an N-&agr;-amino protected amino acid fluoride in situ by reacting an N-&agr;-amino protected amino acid with an ionic fluoride salt in the presence of a peptide coupling agent. It is also directed to the use of the amino acid fluoride thus formed in peptide synthesis.

Abstract: This invention is directed to a process for preparing a pseudotetrapeptide of formula I or a salt or prodrug thereof wherein is optionally nitrogen protected azaheterocyclyl; is a single or double bond; q is 1-5; B is alkyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, aryl, aralkyl, alkylaryl, or alkylaralkyl; Q2 is H or a carboxylic acid protecting group; J is —H, alkyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl; L is OR1, or NR1R2, where R1 and R2 are independently —H, alkyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, aryl, aralkyl, alkylaryl or alkylaralkyl; and p is 1 or 2 which comprises the coupling of two dipeptides or psuedopeptides.

Abstract: The present invention is directed to the use of a soluble polyvalent support for the preparation of combinatorial libraries of compounds. The resultant combinatorial libraries are useful in screening for biologically active moieties in the drug discovery process or in developing compounds with desired physical and chemical properties.

Abstract: This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

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: Novel inhibitors of retroviral protease, e.g., HIV protease, are provided which are peptides having from about 4 to about 8 amino acid residues and which are substrates for said protease derived from known cleavage sites and modified to contain an internal CH.sub.2 NH bond isostere.

Abstract: A process employs amidine or amidine base and a metal compound in the presence of an alcohol or water to transesterify, or saponify esters or amides. Since the process employs relatively mild conditions, it is especially suitable for the production of optically active substances and biomolecules, e.g. peptides, amino acids and nucleic acids which are sensitive to elevated temperatures, extreme pH values and/or long reaction times since these compounds are easily racemised or denatured. The conditions additionally find use in solid phase systems. When amino acid or peptide esters are saponified, the splitting is brought about with lithium hydroxide alone under mild conditions. The use of an amidine base, more particularly DBU or DBN, in combination with the metal salt additionally accelerates the reaction so strongly that even sensitive acid derivatives can be reacted under mild conditions.

Abstract: This invention relates to a novel process for the synthesis of vasoactive intestinal peptide analog Ac(1-31)--NH.sub.2 from four protected peptide fragments.

Abstract: This invention provides Ddz-amino acid pentafluorophenyl esters and Ddz-amino acid 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (ODhbt) esters and their side-chain protected derivatives. Preferred esters and derivatives are crystalline solids. The invention also provides (.alpha.,.alpha.-Dimethyl-3,5-dimethoxybenzyl)-p-methoxycarbonylphenylcarb onate, an improved reagent for the introduction of the Ddz group. Pfp and ODhbt esters of this invention have favorable coupling to racemization ratios and are particularly suited for automated solid-phase peptide synthesis. The invention relates in addition to methods of making the esters of this invention and to methods of using these esters in peptide synthesis.

Abstract: A solid phase peptide synthesis reactor system and method of operating the reactor are provided. The reactor system includes a basket rotatable about an axis within a housing and a receiver which delivers fluid to, and collects fluid from, the housing. The basket has a perforate side wall against which a resin cake for the peptide synthesis is formed. The reactor and receiver form a loop or circuit through which solutions are circulated. The circulation of the solutions prevents the reactor from flooding so that the basket will not be submerged in solution and allows for the use of less liquid. Thus greater amino acid concentrations may be used. The method includes forming a resin cake of uniform depth on the wall of the spinning basket and spraying the solutions against the resin cake while spinning the basket. The solutions will pass through the resin cake and drain to the receiver to be circulated or recycled through the system or discharged from the system.

Abstract: The present invention relates, first, to methods for the synthesis of peptides, in particular T-20 (also referred to as "DP-178"; SEQ ID NO:1) and T-20-like peptides. Such methods utilize solid and liquid phase synthesis procedures to synthesize and combine groups of specific peptide fragments to yield the peptide of interest. The present invention further relates to individual peptide fragments which act as intermediates in the synthesis of the peptides of interest (e.g., T-20). The present invention still further relates to groups of such peptide intermediate fragments which can be utilized together to produce full length T-20 and T-20-like peptides.

Abstract: The invention relates to improved liquid phase processes for the preparation of the 21 residue protein component, (Lys-Leu.sub.4).sub.4 -Lys, of the pulmonary surfactant KL-4. These process are amenable to large scale synthesis and one process employs a method of saponifying an ester which reduces the inherent racemization of the .alpha.-carbon.

Abstract: The invention relates to novel cyclopeptides of the formula Icyclo-(nArg-nGly-nAsp-nD-nE) I,in whichD and E in each case independently of one another are Gly, Ala, .beta.-Ala, Asn, Asp, Asp(OR), Arg, Cha, Cys, Gln, Glu, His, Ile, Leu, Lys, Lys(Ac), Lys(AcNH.sub.2), Lys(AcSH), Met, Nal, Nle, Orn, Phe, 4-Hal-Phe, homo-Phe, Phg, Pro, Pya, Ser, Thr, Tia, Tic, Trp, Tyr or Val, which amino acid residues can also be derivatized,R is alkyl having 1-18 carbon atoms,Hal is F, Cl, Br, I,Ac is alkanoyl having 1-10 carbon atoms, aroyl having 7-11 carbon atoms or aralkanoyl having 8-12 carbon atoms,n denotes no substituent or an alkyl radical R, benzyl or an aralkyl radical having 7-18 carbon atoms on the alpha-amino function of the relevant amino acid residue,with the proviso that at least one amino acid residue has a substituent n and that, where residues of optically active amino acids and amino acid derivatives are involved, both the D and the L forms are included, and also their physiologically acceptable salts.

Abstract: This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides and peptides. The method lends itself to automation and is ideally suited for large scale manufacture oligonucleotides with high efficiency.

Abstract: Disclosed is a method for preparing a photosensitive peptide which is capable of being activated or deactivated in a biological system, including the steps of: (a) providing an amino acid including a photolabile molecule; and (b) incorporating the amino acid into a peptide during synthesis, wherein incorporation of the amino acid into the peptide produces a photosensitive peptide. Also disclosed is a method of introducing a photosensitive cleavage site into a synthetic peptide, including synthesizing a synthetic peptide having at least one photolabile amino acid, wherein the photolabile amino acid is positioned within the synthetic peptide so that upon irradiation the synthetic peptide is cleaved.

Abstract: A process for preparing and purifying cyclic peptides having disulfide moieties in a two step processing operation including reverse phase chromatography which simplifies synthesis and reduces production costs, yet produces high, quality yield. The improved process is particularly useful for the preparation of vasopressin and oxytocin and their respective derivatives and analogs.

Abstract: Compounds of the present invention include cell growth inhibitors which are peptides of Formula IA--B--D--E--F--G (I)and acid salts thereof, wherein A, D, and E are .alpha.-amino acid residues, B is an .alpha.-amino acid residue or an .alpha.-hydroxy acid residue, F is an aminobenzoic acid residue or an aminocycloalkanecarboxylic acid residue, and G is a monovalent radical, such as, for example, a hydrogen atom, an amino group, an alkyl group, an alkylene alkyl ether, an alkylene alkyl thioether, an alkylene aldehyde, an alkylene amide, a .beta.-hydroxylamino group, a hydrazido group, an alkoxy group, a thioalkoxy group, an aminoxy group, an oximato group, an alkylene aryl group, an alkylene ester, an alkylene sulfoxide or an alkylene sulfone. Another aspect of the present invention includes pharmaceutical compositions comprising a compound of Formula I and a pharmaceutically acceptable carrier.

Abstract: A process for preparing pentapeptides of the formula I ##STR1## where A and R.sup.1 -R.sup.3 have the stated meanings, comprises assembling the pentapeptide stepwise starting from a prolinamide of the formula II ##STR2## where R.sup.1 and R.sup.2 have the abovementioned meanings, and eliminating the group --NR.sup.1 R.sup.2 by hydrolysis where appropriate the peptide obtained in this way.

Abstract: The present invention relates to a peptide having an amino acid sequence of Val-Val-Tyr-Pro as well as an agent for inhibiting elevation of triglyceride levels in blood, a food for specified health use (the so-called physiologically functional food) and a feed comprising the above peptide as an active component. According to the present invention, a peptide inhibiting elevation of triglyceride levels in blood as well as an agent for inhibiting elevation of triglyceride levels in blood, a physiologically functional food and a feed, all comprising the peptide as an active component are obtained. With these products of the invention, it becomes possible to prevent or treat obesity and hyperlipemia of human and animals as well as circulatory system diseases such as hypertension and arteriosclerosis associated therewith. Furthermore, the materials of the invention make it possible to improve the meat quality of livestock and hatchery fish.

Abstract: A method for synthesizing a water-soluble .beta.-sheet forming peptide having at least about 35% amino acids having hydrophobic side chains, the method comprising linking amino acids having charged side chains and amino acids having noncharged polar side chains with amino acids having hydrophobic side chains, wherein the amino acids having charged side chains are provided in a ratio of at least about 2:1 amino acids having positively charged side chains to amino acids having negatively charged side chains; wherein the peptide is water soluble under physiological conditions and forms .beta.-sheet structures.

Abstract: There is disclosed a novel process for preparing aza cyclohexapeptides of the formula ##STR1## where all variables are defined herein.

Abstract: The present invention provides cyclic peptides having broad spectrum antimicrobial activity. The peptides exhibit improved efficacy, bioavailability and/or serum half-life as compared with non-cyclized analogues.

Abstract: A peptide is provided for use as a diagnostic imaging, radiotherapeutic, or therapeutic agent, which peptide has a conformationally constrained global secondary structure obtained upon complexing with a metal ion. The peptide is of the general formula:R.sub.1 --X--R.sub.2where X is a plurality of amino acids and includes a complexing backbone for complexing metal ions, so that substantially all of the valances of the metal ion are satisfied upon complexation of the metal ion with X, resulting in a specific regional secondary structure forming a part of the global secondary structure; and where R.sub.1 and R.sub.2 each include from 0 to about 20 amino acids, the amino acids being selected so that upon complexing the metal ion with X at least a portion of either R.sub.1 or R.sub.2, or both, have a structure forming the balance of the conformationally constrained global secondary structure.

Abstract: Compounds of the formula ##STR1## where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the meaning stated in the description, and a process for preparing them are described. The compounds are suitable as starting material for synthesizing substances which are active against tumors.

Abstract: This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides and peptides. The method lends itself to automation and is ideally suited for large scale manufacture oligonucleotides with high efficiency.

Abstract: The compound Me.sub.2 Val--Val--MeVal--Pro--Pro--NHBzl.multidot.HCl is described. It is prepared from Z--Val--Val--MeVal--Pro--OR.sup.1 where Z and R.sup.1 have the meanings stated in the description. The compound shows antineoplastic activity.

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: This invention is directed to tetrahydronaphthalene compounds of the formula ##STR1## wherein R.sup.1 is hydrogen, bromine, cyano, formyl, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, aryloxy, lower aralkoxy or aryl; R.sup.2 is an amino acid residue or a chain of 2 to 20 amino acid residues wherein reactive moieties in the side chains of the amino acid residue(s) is/are protected or unprotected, and wherein the amino group of the N-terminal amino acid is a free or protected amino group; A.sup.1, A.sup.2, A.sup.3 and A.sup.4 each are .alpha.-amino acid residues wherein A.sup.1 and A.sup.2 are in the L configuration and A.sup.3 and A.sup.4 are in the D configuration when the .alpha.-C atom of said .alpha.-amino acid residue is asymmetric; X is oxygen or sulphur; Y is a residue of the formula ##STR2## n is 0 or 1; R.sup.3 is hydrogen or lower alkyl; R.sup.

Abstract: The invention is directed to systematic synthetic and testing strategies for .alpha.-keto acids, esters and amides. The method of synthesis comprises (A) reacting (cyanomethylene)triphenylphosphorane with a carbonyl compound selected from carboxylic acids (RCOOH) and acyl chlorides (RCOCl) to make a cyano keto phosphorane, (B) oxidizing said phosphorane and (C) reacting the oxidized product with a nucleophile (NuH) to make the product .alpha.-keto acid, ester or amide. Systematic synthesis and testing are achieved by a modular approach in which arrays of molecules are generated by variation of R and Nu.

Abstract: A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two "sub-monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic is displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a resin-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like.

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 is 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: A method for synthesizing conformationally restricted amino acids, peptides, and peptidomimetics by ring closing metathesis. The method includes the steps of synthesizing a peptide precursor containing first and second unsaturated C--C bonds and contacting the peptide precursor with a RCM catalyst to yield a conformationally restricted peptide. Suitable peptide precursors may contain two or more unsaturated C--C bonds. These bonds may be olefinic bonds and may be contained in first and second alkenyl groups which may be allyl groups. The RCM catalyst may be a Ruthenium or Osmium carbene complex catalyst and more specifically, a Ruthenium or Osmium carbene complex catalyst that includes a Ruthenium or Osmium metal center that is in a +2 oxidation state, has an electron count of 16, and is pentacoordinated. The method may be carried out using solid-phase-peptide-synthesis techniques.

Abstract: The present invention relates to a reaction and dissolving medium for the synthesis of peptides. This reaction and dissolving medium for peptide synthesis and/or purification comprises a diluent A chosen from a group of water-immiscible solvents and a phenol B. This peptide synthesis can be used to synthesize medicaments, vaccines, agro-foodstuff products or plant protection products.

Abstract: The present invention relates to a method for the preparation of polyamino acids, with controlled molecular weights, by polymerization of N-carboxyanhydrides (NCAs) of at least one amino acid, using at least one initiator of the strong base type and in liquid medium, characterized in that it consists in including, in the liquid reaction medium, given amounts of water and/or of alcohol. Application: synthesis of polyamino acids with mechanical and rheological characteristics adapted to applications as biomaterials.

Abstract: A method for peptide synthesis using an N-?N'-nitroso-(R')carbamoyl!amino acid as the starting compound. The compound is separated into N.sub.2, R'OH and N-carboxyanhydride of formula (II). ##STR1## The compound (II) together with an amino acid or peptide with at least one free .alpha.-amino function is introduced into a reactive medium to obtain a dipeptide or a higher peptide than the added peptide.