Abstract: Linear peralkylated oligopeptide sets of molecules are disclosed, as are their methods of synthesis and use in acceptor binding assays. Each molecule or chain of a set contains the same number of two to about ten substituted peralkylated amino acid residues, and the member chains of a set are present in equimolar amounts. The chains of a set contain one or more predetermined peralkylated amino acid residues at one or more predetermined positions of the peralkylated oligopeptide chain. The set contains equimolar amounts of at least six different peralkylated amino acid residues at one or more of the same predetermined positions of the peralkylated oligopeptide chain.

Abstract: Disclosed herein are peptidomimetic compounds of the formula A--B--D--CH.sub.2 CH{CH.sub.2 C(O)R.sup.1 }C(O)--NHCH{CR.sup.2 (R.sup.3)COOH}C(O)--E wherein A is a terminal group, for example an optionally substituted phenylalkanoyl, and B is a N-methyl amino acid residue; or A and B together form a saturated or unsaturated alkylaminocarbonyl; D is an amino acid residue; R.sup.1 is alkyl, cycloalkyl, a monosubstituted or a disubstituted amino; R.sup.2 is hydrogen and R.sup.3 is phenylalkyl, or R.sup.2 and R.sup.3 are joined to form a cycloalkyl; and E is a terminal unit, for example, an alkylamino or a monovalent amino acid radical such as NHCH(alkyl)C(O)OH. The derivatives are useful for treating herpes infections.

Abstract: The invention provides compounds of the general formula (I):A.sup.1 --B.sup.1 --X.sup.1 --(CH.sub.2).sub.m --(CON(R.sub.1)).sub.r --(CH.sub.2).sub.s --Y.sup.1 --(CH.sub.2).sub.s --(N(R.sub.1)CO).sub.r --(CH.sub.2).sub.n --X.sup.1 --B.sup.1 --A.sup.1The compounds of this invention are also illustrated by the Formula (II):A.sup.2 --B.sup.2 --X.sup.2 --(CH.sub.2).sub.m --(N(R.sub.1)CO).sub.r --(CH.sub.2).sub.s --Y.sup.2 --(CH.sub.2).sub.s --(CON(R.sub.1)).sub.r --(CH.sub.2).sub.n --X.sup.2 --B.sup.2 --A.sup.2The compounds have hemoregulatory activities and can be used to stimulate haematopoiesis and for the prevention and treatment of viral, fungal and bacterial infectious diseases.

Abstract: Antagonists of neurokinin A which are derivatives of naturally occurring neurokinin A in which the amide bond connecting the two amino acids on the carboxy terminal end is modified are described. The antagonism is confirmed using conventional competitive binding and biochemical assays as well as conventional physiological tests and the use of these derivatives in a variety of conditions in which neurokinin A is implicated is also described.

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: A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain alkylamine side chains.

Abstract: Disclosed are peptides and peptide mimetics that bind selectins, including endothelial leukocyte adhesion molecule 1 (ELAM-1). Such peptides and peptide mimetics are useful in methods for blocking adhesion of leukocytes to the selectins for the purpose of inhibiting inflammation as well as in diagnostic methods employing labeled peptides and peptide mimetics that bind selectins for the purpose of determining the site of inflammation in mammals which inflammation is mediated by the presence of one or more selectins.

Abstract: An improved method for isolating and purifying a glutathione derivative is disclosed. More particularly, the invention provides a method for isolating and purifying S-(1, 2-dicarboxyethyl)glutathione or its pharmacologically acceptable salt from a reaction mixture available upon reacting glutathione or its salt with either fumaric acid or its salt or maleic acid or its salt, which comprises a first step of converting the S-(1, 2-dicarboxyethyl)glutathione or salt thereof in the reaction mixture to the corresponding copper salt, dissolving the copper salt in an aqueous solution of acetic acid, formic acid or propionic acid, and removing the contaminant glutathione, oxidized glutathione and fumaric acid copper salts with the aid of activated carbon and a second step of dissolving or suspending the isolated S-(1,2-dicarboxyethyl)glutathione copper salt in water and blowing hydrogen sulfide gas through the resulting aqueous solution or suspension to remove copper.

Abstract: The invention concerns compositions containing a lanthionine containing bacteriocin such as nisin which are stabilized by the presence of a thioether stabilizing agent against degradation.

Abstract: A linear peptide which is an analog of a naturally occurring, biologically active peptide having an active site and a binding site responsible for the binding of the peptide to a receptor on a target cell, cleavage of a peptide bond in the active site to the naturally occurring peptide being unnecessary for in vivo biological activity, the analog having a non-peptide bond instead of a peptide bond between an amino acid of the active site and an adjacent amino acid, and having the same binding site as the naturally occurring peptide, so that the analog is capable of acting as a competitive inhibitor of the naturally occurring peptide by binding to the receptor and, by virtue of the non-peptide bond, failing to exhibit the in vivo activity of the naturally occurring peptide.

Abstract: This invention provides novel reagents for the preparation of radiopharmaceuticals useful as imaging agents for the diagnosis of cardiovascular disorders, infection, inflammation and cancer, diagnostic kits comprising said reagents and intermediate compounds useful for the preparation of said reagents. The reagents are comprised of stable hydrazone modified biologically active molecules that react with gamma emitting radioisotopes to form radiopharmaceuticals that selectively localize at sites of disease and thus allow an image to be obtained of the loci using gamma scintigraphy.

Abstract: This invention provides new antifungal compounds of Formula I or II: ##STR1## wherein R, R.sup.1 and R.sup.2 are defined in the specification produced by culture LL-15G256 (Hypoxylon oceanicum), NRRL 21363 and their production by fermentation and use as antifungal agents.

Abstract: Compounds of the invention inhibit urokinase plasminogen activator: ##STR1## where R.sub.1 is lower alkyl, lower alkenyl, lower alkynyl, aryl, aralkyl, aryl-alkenyl, aryl-alkynyl, aryl-cycloalkyl, unsubstituted or substituted with 1-3 halo, OH, NH.sub.2, lower alkyl, halo-lower alkyl, lower alkoxy, lower alkylamino, lower alkylthio, CN or NO.sub.2 ;R.sub.2 is aryl or aralkyl, unsubstituted or substituted with 1-3 halo, OH, NH.sub.2, CN, NO.sub.2, lower alkyl, halo-lower alkyl, lower alkoxy, lower alkylamino, lower alkylthio, or cycloalkyl;R.sub.3, R.sub.5 and R.sub.9 are each independently H or lower alkyl;R.sub.4 is ##STR2## where R.sub.6 and R.sub.7 are each independently H, OH, NH.sub.2, CN, NO.sub.2, lower alkyl, halo-lower alkyl, lower alkoxy, lower alkylamino, lower alkylthio, or cycloalkyl, and n and m are each independently an integer from 1 to 3 inclusive; and pharmaceutically acceptable acid addition salts thereof.

Abstract: The present invention provides compositions and methods of inhibiting or inducing activation of T cells in a patient. The methods comprise administering a therapeutically effective dose of pharmaceutical compositions comprising a pharmaceutically acceptable carrier and peptides of between about 4 and about 20 residues, that bind antigen binding sites on MHC molecules encoded by substantially all alleles of a DR locus. These peptides are referred to as pan DR binding peptides. The pan DR binding peptides can be used to inhibit immune responses associated with immunopathologies, such as autoimmunity, allograft rejection and allergic responses. The peptides can also be used in combination with CTL peptides to enhance a CTL response.

Abstract: The present invention is directed to novel ketomethylene group-containing aldehyde inhibitors of cysteine or serine proteases. Methods for the use of the protease inhibitors are also described.

Abstract: The present invention relates to certain peptide derivatives, as described herein, which are human leukocyte elastase (HLE) inhibitors making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of diseases in mammals in which HLE is implicated, including treatment of tissue degenerative diseases such as pulmonary emphysema. The invention also includes intermediates useful in the synthesis of these peptide derivatives, processes for preparing them, pharmaceutical compositions containing such peptide derivatives and methods for their use.

Abstract: Novel compounds having activity against trypsin are disclosed. Specifically, novel peptide aldehyde analogues that have substantial potency and specificity as inhibitors of mammalian pancreatic trypsin are presented. The compounds are useful in the prevention and treatment of the tissue damage or destruction associated with pancreatitis.

Abstract: This invention relates to oxazolidine inhibitors of calpain and/or cathepsin B and to compositions containing them. As inhibitors of calpain and/or cathepsin B, the compounds are useful in the treatment of patients afflicted with acute or chronic neurodegenerative disorders.

Abstract: Novel compounds of the formula I ##STR1## in which R.sup.1 and R.sup.2 are hydrogen, C.sub.1 -C.sub.4 alkyl or are linked to form C.sub.3 -C.sub.7 cycloalkyl and R.sup.3, R.sup.4 and R.sup.5 are the same or different and are hydrogen, C.sub.1 -C.sub.4 alkyl, hydroxy, OR.sup.6, SR.sup.6, halogen, NR.sup.7 R.sup.8, NO.sub.2, CN, CONR.sup.7 R.sup.8 or CO.sub.2 R.sup.9 wherein R.sup.6 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.10 aralkyl and R.sup.7, R.sup.8 and R.sup.9 are the same or different and are hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.10 aralkyl or R.sup.7 and R.sup.8 together with the nitrogen atom to which they are bound form 5 or 6 membered azacycloalkyl or oxazacycloalkyl; Arg is arginine ?NH--CH(CH.sub.2 CH.sub.2 CH.sub.2 NH--C(.dbd.NH)--NH.sub.2)--CO!; X is methine CH or nitrogen; n is an integer from 0 to 7; L is a peptide linker, and H is the carboxy terminal end of hirudin, and salts thereof, are provided.

Abstract: Compounds which Inhibit interleukin-1.beta. protease activity, pharmaceutical compositions containing the compounds and methods using the compounds are provided. The compounds have the formula ##STR1## wherein n is 0-2; each AA is Independently L-valine or L-alanine;R.sub.1 is selected from the group consisting of N-?4(N,N-dimethylaminomethyl)!benzoyl, N-benzoyloxycarbonyl, N-methyl-N-?4-(pyridyl)methyl!, N-?4-(pyddyl)methyl!carbonyl, N-3-(piperidinopropionyl), N-?4-(morpholinoethoxy)benzoyl, N-2-(quinuclidinyl)carbonyl, N-(3-pyridyl)methoxy carbonyl, N-(2-pyddyl)methoxy carbonyl, N-methyl-N-benzyl carbonyl, N-methyl-N-?2-(4-pyridyl)ethyl!carbonyl, and N-(N-phenylpiperazino) carbonyl; andR.sub.8, R.sub.9 and R.sub.10 are as defined below.

Abstract: An enzyme reaction stabilizer consisting of poly-L-lysine or its salt as an effective constituent, a method for using the enzyme reaction stabilizer, and an enzyme preservative consisting of poly-L-lysine or its salt as an effective constituent are disclosed in this invention. While enzyme reactions are carried out, the enzyme reaction stabilizer and the method for using it prevents both the deactivation of enzymes due to the proliferation of included microorganisms and the decomposition of the reaction products and there is an advantage in that the enzyme reaction stabilizer can easily be separated from the reaction products. On the other hand, while the enzyme solution is preserved, the enzyme preservative of this invention prevents the deactivation of the enzyme due to the proliferation of included microorganisms in the enzyme solution or the enzyme preserving solution.

Abstract: The invention is a branched synthetic peptide conjugate which can be designed to bind to a target cell surface receptor, to penetrate into target cells, and to deliver a diagnostic probe or cytotoxic functionality to a desired site of action. The invention provides a relatively small molecule of flexible design having a branched structure for systematically incorporating a desired number of cytotoxic functions, peptide-based localization signals or diagnostic probes. The invention addresses problems associated with protein-based therapeutic or diagnostic agents.

Abstract: The present invention relates to UCK14 compounds having antitumor activity which are represented by the formula: ##STR1## wherein R.sup.1 is hydrogen or --COOC(CH.sub.3).sub.3 ; and R.sup.2 and R.sup.3 are taken together to form --CH.sub.2 --, or each R.sup.2 and R.sup.3 independently are hydrogen,and pharmaceutically acceptable salts thereof.

Abstract: The present invention is directed to a compound of the formula: ##STR1## or a pharmaceutically acceptable addition salt thereof, wherein C.sup.3 and C.sup.2 in combination have the configuration S,R or R,S;wherein Y is straight or branched chain lower alkyl having 1 to 6 carbon atoms, straight or branched chain lower alkenyl or alkynyl having 2-6 carbon atoms, cyclic alkyl or alkenyl having 5 or 6 carbon atoms, or benzyl; andwherein X is an amino acid or an oligopeptide having from 1 to 8 amino acid residues, the first amino acid residue at the N-terminus of X being a natural or a synthetic L-amino acid having a radius of gyration of less than 1.54 .ANG., X also having a carboxyl or a carboxyamide moiety at its carboxy terminus. The present invention is further directed to a pharmaceutical composition and to a method of inhibiting bradykinin degradation in a patient using the above-described compound.

Abstract: Amphiphilic derivatives of amino acids or peptides are provided, comprising a polyhydroxylated hydrophilic part derived from a sugar, from a polyol, from an aminopolyol or from an oligosaccharide, and at least one hydrophobic part derived from a hydrocarbon, fluorocarbon, or a mixed fluorocarbon/hydrocarbon, saturated or unsaturated, having from 5 to 20 carbon atoms, the hydrophobic part(s) being linked to the hydrophilic part by a junction bearing an amino acid or a peptide.

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: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, AIDS and autoimmune diseases.

Abstract: Peptidomimetics of the formula C-AMBA-X where C is cysteine, X is, for example, methionine or phenylalanine and AMBA is a hydrophobic spacer, notably 3-aminomethylbenzoic acid. These compounds are effective inhibitors of p21 ras farnesyltransferase. Other modifications including alternative spacers for AMBA, and replacement of the A.sub.1 A.sub.2 X component of known CA.sub.1 A.sub.2 X tetrapeptides by a non-peptide aryl or heterocyclic component are also disclosed as are various phosphonylated and arylated derivatives of peptides and peptidomimetics. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also referred to.

Abstract: Compounds which inhibit interleukin-1.beta. protease activity, pharmaceutical compositions containing the compounds and methods using the compounds are provided. The compounds have the formula ##STR1## wherein n is 0-2; each AA is independently L-valine or L-alanine; R.sub.1 is selected from the group consisting of N-[4-(N,N-dimethylaminomethyl)]benzoyl, N-benzyloxycarbonyl, N-methyl-N-[4-(pyridyl)methyl], N-[4-(pyridyl)methyl]carbonyl, N-3-(piperidinopropionyl), N-[4-(morpholinoethoxy)benzoyl, N-2-(quinuclidinyl)carbonyl, N-(3-pyridyl)methoxy carbonyl, N-(2-pyridyl)methoxy carbonyl, N-methyl-N-benzyl carbonyl, N-methyl-N-[2-(4-pyridyl)ethyl]carbonyl, and N-(N-phenylpiperazino)carbonyl; and R.sub.8, R.sub.9, R.sub.10 are each independently hydrogen, lower alkyl, halo substituted methyl, carbalkoxy, benzyl, phenyl, or phenyl mono or disubstituted with fluoro, nitro, methoxy, chloro, trifluoromethyl or methanesulfonyl.

Abstract: This invention relates to novel peptides and mixtures thereof useful for detecting HCV infections. These peptides are also useful as active ingredients in vaccines against HCV infection.

Abstract: The invention relates to peptide compounds of formula (I):R.sub.1 --A--Gly--Asp--Trp--R.sub.2 (I)in which R.sub.1, R.sub.2 and A are as defined in the description, and anti-aggregation medicaments containing the same.

Abstract: Use of 7-amino-L-glycero-L-gulo-2,6-anhydro-7-desoxy-heptonic acid and 2-benzoxycarbonylamino-0.sup.1 -methyl-2-desoxy-.beta.-glucopyranuronic acid, their derivatives and the enantiomorphous compounds for incorporation and for manufacture in pharmacologically active peptide hormones.

Abstract: Disclosed herein is a combination of an antiviral nucleoside analog and a ribonucleotide reductase inhibiting peptide derivative. The combination is useful for combatting herpes infections.

Abstract: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, and autoimmune diseases.

Abstract: An antiinflammatory, antiallergic or hepatic disorders inhibitory agent containing a compound of the following formula or a pharmaceutically acceptable salt thereof as an active ingredient ##STR1## (wherein n represents 0 or 1; R.sub.1 means hydrogen or an alkyl group; R.sub.2 and R.sub.3 are the same or different and independently mean a hydroxyl group, a lower alkoxy group or an amino group or R.sub.2 and R.sub.3 together form an imino group; provided that R.sub.1 means an alkyl group where n=0 and R.sub.2 and R.sub.3 are the same or different and independently mean a hydroxyl group or a lower alkoxy group).

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin, as well as related compounds, are described. Articles of manufacture useful in pretargeting methods are also discussed.

Abstract: A method for the separation of at least one specific binding entity from a mixture of binding entities, which comprises the steps of contacting said mixture of binding entities with an immobilized peptide in which said peptide specifically binds to said specific binding entity, and separating the immoblized peptide/specific binding entity complex from the mixture of binding entities; an immobilized peptide-solid support preparation comprising a cleavable link between the peptide and the solid support, and a method for the preparation of a peptide from an immobilized peptide-solid support preparation.

Abstract: A polymer conjugate consisting essentially of: from 90 to 99.9 mol % of units represented by the formula ##STR1## from 0.1 to 5 mol % of units represented by the formula ##STR2## wherein one of R.sub.1 and R.sub.2 is a copolymer residue of the formula ##STR3## and the other one is hydrogen atom; from 0 to 9.9 mol % of units represented by the formula ##STR4## wherein R is a phenyl or t-butoxy group, R.sub.3 is H or an acetyl group, A and A.sub.1 which may be the same or different, represent a chemical single bond, an amino acid residue or peptide spacer selected from .beta.Ala, Gly, Phe-Gly, Phe-Phe-, Leu-Gly, Val-Ala, Phe-Ala, Leu-Phe, Leu-Ala, Phe-Leu-Gly, Phe-Phe-Leu, Leu-Leu-Gly, Phe-Tyr-Ala, Phe-Gly-Phe, Phe-Phe-Gly, Phe-Leu-Gly-Phe, Gly-Phe-Leu-Gly-Phe,Gly-.beta.Ala, Phe-Gly-.beta.Ala, Phe-Phe-.beta.Ala, Leu-Gly-.beta.Ala, Val-Ala-.beta.Ala, Phe-Ala-.beta.Ala, Leu-Phe-.beta.Ala, Leu-Gly-.beta.Ala, Phe-Leu-Gly-.beta.Ala, Phe-Phe-Leu .beta.Ala, Leu-Leu-Gly-.beta.Ala, Phe-Tyr-Ala-.beta.Ala, Phe-Gly-Phe-.

Abstract: A compound of the formula: ##STR1## wherein R.sup.1 is aryl, or a group of the formula: ##STR2## wherein X is CH or N, and Z is O or N--R.sup.5,in which R.sup.5 is hydrogen or lower alkyl,R.sup.2 is hydroxy or lower alkoxy,R.sup.3 is hydrogen or lower alkyl which may have suitable substituent(s),R.sup.4 is ar(lower)alkyl which may have suitable substituent(s),A is carbonyl or sulfonyl, andY is a bond or lower alkenylene,and pharmaceutically acceptable salt thereof. The disclosed compounds are useful for treating respiratory diseases such as bronchaedema.

Abstract: Pseudopeptide compounds based on a modified bradykinin sequence are potent bradykinin receptor antagonists. Amino acids at postions 2 through 5 are replaced by olefinic aminoalkenoyl groups to reduce the peptidic nature of the compounds.The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract: The present invention relates to a process for manufacturing a composition highly containing .alpha.-lactalbmin. This process comprises adjusting, to pH of 2-4 or 5 or higher, cheese whey, acid casein whey or rennet casein whey; contacting the whey with an ion exchanger, to produce an exchanger-passed solution; and then, concentrating and/or desalting the exchanger-passed solution, if necessary after the exchanger-passed solution is adjusted to a pH of 4 or lower. According to the present process, it is possible to efficiently produce a high .alpha.-lactalumin content composition at low cost and in a simple and easy manner on an industrial scale. The resultant high .alpha.-lactalumin content composition can be used for food materials and medical materials.

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: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, and autoimmune diseases.

Abstract: A lipolytic enzyme inhibitor is disclosed which comprises as an active ingredient at least one of a basic protein, a basic polypeptide and salt thereof. The inhibitor is useful as a dieting agent for the prevention of obesity and lipemia and as an additive for food and feed.

Abstract: The invention relates to novel derivatives of peptides usable as inhibitors of bacterial collagenases.These derivatives comply with the formula: ##STR1## in which R.sup.1 is an optionally substituted aryl or aralkyl group or the group ##STR2## with R.sup.6 being the side chain of an .alpha.-amino acid and R.sup.7 R.sup.8 a protective group or a radical derived from an amino acid or a protected peptide, R.sup.2 is derived from proline, hydroxyproline, thiazolidine or dehydroproline, R.sup.3 is H or an alkyl, and R.sup.4 is the side chain of an amino acid and R.sup.5 and R'.sup.5 are H, a metal, an alkyl or benzyl.The derivatives in which R'.sup.5 is a metal or hydrogen can be used as inhibitors of bacterial collagenases.

Abstract: Carboxyalkylcarbonyl aminoacid inhibitors of endopeptidases of the formula: ##STR1## or pharmaceutically acceptable salt thereof, wherein R.sup.1 is H, alkyl, arylalkyl, aryl or aryloxyalkyl; R.sup.2 is alkyl, alkenyl, alkynyl, alkoxy or alkylthio, wherein the alkyl portion is substituted with 0-3 substituents independently selected from the group consisting of hydroxy, alkoxy, alkoxyalkoxy, alkylthio, aryl, alkoxyalkylthio, arylalkoxy and arylalkylthio; R.sup.3 and R.sup.4 are independently alkyl or arylalkyl; or R.sup.3 and R.sup.4 together with the carbon to which they are attached form an optionally substituted 5-, 6- or 7-membered ring wherein said ring comprises 0 to 1 heteroatoms selected from the group consisting of sulfur and oxygen; R.sup.5 is H, alkyl, alkoxyalkyl, alkylthioalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylalkoxyalkyl or arylalkylthioalkyl; R.sup.

Abstract: A method of treating medical conditions with proteinase inhibitors of the formula: ##STR1## wherein B is H or an amino acid blocking group for the N-terminal amino acid nitrogen;R.sub.1 is an optionally protected .alpha.-amino acid side chain such that P.sub.2 is the residue of an .alpha.-amino acid selected from the group consisting of phenylalanine (Phe), leucine (Leu), tyrosine (Tyr) and valine (Val), and substituted analogs thereof, particularly including Tyr(OMe);R.sub.2 is an optionally protected .alpha.-amino acid side chain such that P.sub.1 is the residue of an .alpha.

Abstract: Compositions which are immunologically crossreactive with antibodies are provided, together with preparative and therapeutic methods therefor. The compositions preferably comprise a plurality of covalently bound synthetic compounds, at least one of which is individually crossreactive with at least one complementarity determining region (CDR) of the antibody. Preferred processes for preparing the immunologically crossreactive compounds comprise identifying chemical functionality such as hydroxyl groups in the CDR which participates in at least one immunological binding phenomena, determining the three-dimensional positioning of the chemical functionality, and synthesizing a compound which comprises substantially the same chemical functionality as the CDR and which has at least one conformation wherein the three-dimensional positioning of the chemical functionality is substantially identical to the three-dimensional positioning of the chemical functionality of the CDR.

Abstract: Novel diamino acid derivative dual inhibitors of neutral endopeptidase and angiotensin converting enzyme of the formula ##STR1## wherein: Z is amino, lower alkylamino, di-(lower alkyl)amino R.sup.9 C(O)NH-- or an optionally substituted guanidino group;R.sup.1 is hydrogen or R.sup.7 R.sup.8 N--;R.sup.2 is hydrogen, lower alkyl, cyclolower alkyl, aryllower alkyl or heteroaryllower alkyl; and R.sup.3 is hydrogen, lower alkyl or cyclolower alkyl; or R.sup.2 and R.sup.3, together with the carbon to which they are attached, comprise a 3-7 membered carboxyclic ring;R.sup.4 is hydrogen, lower alkyl, aryl lower alkyl or heteroaryllower alkyl;R.sup.5 and R.sup.6 are independently hydroxy, lower alkoxy, amino, aryllower alkoxy, lower alkylamino and di-(lower alkyl)amino;R.sup.7 is R.sup.9 C(O)-- or R.sup.10 SO.sub.2 --; and R.sup.8 is hydrogen, lower alkyl, aryllower alkyl or aryl; or R.sup.7 and R.sup.8, together with the nitrogen to which they are attached, comprise a 5-7 membered ring;R.sup.

Abstract: The trifluoromethylketone derivatives (I) and pharmaceutically acceptable salts thereof have a human leukocyte elastase inhibiting activity and are useful as human leukocyte elastase inhibitors for treating or preventing degenerative diseases. The trifluoromethylketone derivatives (I) have the following formula: ##STR1## wherein R.sup.1 is C.sub.1-6 alkyl which has one or two substituents selected from carboxy, esterified carboxy and di-C.sub.1-6 alkylcarbamoyl; phenyl(C.sub.1-6) alkyl, the phenyl moiety of which may have halogen or nitro or amino substituents and the alkyl moiety of which may have carboxy or esterified carboxy substituents; halo-phenyl; morpholino; or morpholino(C.sub.1-6) alkyl,R.sup.2 and R.sup.3 are each C.sub.1-6 alkyl,X is -- or --NH--, andY is ##STR2## and pharmaceutically acceptable salts thereof.