Abstract: Methods for the synthesis of &agr;-hydroxy-&bgr;-amino acid and amide derivatives and &agr;-ketoamide derivatives and novel derivatives made by these methods are provided. These methods involve reacting a N-terminally blocked (protected) aminoaldehyde with an isonitrile and a carboxylic acid to give an amino-&agr;-acyloxy carboxamide. The acyloxy group may be removed to give the derivative. Alternatively the protecting group is removed and acyl shift occurs to give the derivative. These derivatives are useful in the synthesis of compounds such as peptidyl &agr;-ketoamides and &agr;-hydroxy-&bgr;-carboxylic acid and amide derivatives. Certain of these compounds have been reported to have activity as inhibitors of proteases, such as serine proteases and cysteine proteases.

Abstract: Methods and compositions are provided which are useful for delivering a biologically active substance to a localized site in vivo and for altering the physical dimensions of a body tissue. These methods and compositions employ protein polymers having varying ratios of elastin-like, collagen-like, keratin-like repeating units and repeating units which promote protein crystallization such as silk-like repeating units. By varying the length of segments of the repeating units and/or the concentration of the protein polymers in the composition, the rate of delivery of a biologically active substance to a localized site can be greatly varied. Moreover, because the compositions are capable of acquiring a non-liquid form under normal physiological conditions, they find use as biocompatible tissue augmentation products.

Abstract: &bgr;-sheet mimetics and methods relating to the same are disclosed. The &bgr;-sheet mimetics have utility as protease and kinase inhibitors, as well as inhibitors of transcription factors and protein-protein binding interactions. Methods of the invention include administration of a &bgr;-sheet mimetic, or use of the same for the manufacture of a medicament for treatment of a variety of conditions associated with the targeted protease, kinase, transcription factor and/or protein-protein binding interaction.

Abstract: The invention concerns pharmaceutically useful peptide derivatives of the formula (I): P—R1—R2—R3—R4, in which P, R1, R2, R3 and R4 have various meanings defined herein, and their pharmaceutically salts, and pharmaceutically compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell medicated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.

Abstract: Specially designed non-mammalian GnRH analog decapeptides resistant to degradation by the placental enzyme, C-ase-1, or a post-proline peptidase, are disclosed. The GnRH analogs are further defined as analogs of Chicken II GnRH or Salmon GnRH. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp at position 6 and ethylamide or aza-Gly-amide at position 10. The D-Arg (6)-Chicken II GnRH-ethylamide, D-Arg (6)-Chicken II GnRH-aza-Gly (10)-amide, the D-Arg (6)-Salmon GnRH ethylamide, and D-Arg (6)-Salmon GnRH-aza-Gly (10)-amide analogs are also provided, and demonstrate preferential binding to chorionic GnRH receptor that is greater relative to the biding of these analogs to pituitary GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparation, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent.

Abstract: &bgr;-Amino-&agr;-hydroxycarboxylic acid derivatives represented by the following formula and salts thereof which are useful as human immunodeficiency virus (HIV) protease inhibitors: The compounds are effective for treating a patient suffering from AIDS and AIDS related diseases.

Abstract: The present invention is directed to novel disulfides and thiols that are of up to about eighteen amino acids. One example, is a compound of the formula (1): A-B-C-S-S-D-E-F, wherein: A and F are selected from the group consisting of hydrogen, an amino acid, a dipeptide, a tripeptide, a modified polypeptide up to three amino acids long, and a carbobenzoxy group, B and E are selected from the group consisting of an amino acid, a dipeptide, a tripeptide, and a modified polypeptide comprising up to and including three amino acids, C and D are selected from the group consisting of a modified polypeptide and a polypeptide comprising up to and including three amino acids, and S is the sulfur atom in the modified polypeptide and the polypeptide in C and D.

Abstract: Synthetic peptide antigen analogues of native peptide antigens with partial or complete retro, inverso or retro-inverso modifications are provided. When administered as an immunogen to an immunocompetent host the synthetic peptide antigen analogues induce the production of antibodies which recognize the native peptide antigen. Uses of these analogues, vaccines and methods of preparing vaccines comprising these antigen analogues, and antibodies generated using these antigen analogues are also provided.

Abstract: Novel chromogenic, fluorogenic and fluorescence polarization substrates which are useful in HCV NS3 protease and inhibitor assays.

Abstract: A depsipeptide containing a non-natural amino acid(s) having the formula (1) wherein R1 represents a C5-C20 alkyl group and others; R2 represents —O—CO—CH(R5)—X—CH(R6)—NH— (wherein X represents N(R7)—CO, CH2—CO, CH2—CH2 and others, R5, R6, and R7 represent a hydrogen atom or a C1-C6 alkyl group); R3 represents and wherein the remaining substituent variables are as defined herein. The above depsipeptides have a promoting activity on the production of apolipoprotein E, and are useful as a therapeutic agent for neurologic damages, especially dementia, and hyperlipemia.

Abstract: A method of stimulating endogenous production of cytokines and hemopoietic factors by introducing to a mammalian body in need of stimulation of cytokines or hemopoietic factors or both, an effective amount of oxidized glutathione and/or its therapeutically beneficial salts, and/or its therapeutically beneficial derivatives, for a period of time to stimulate said endogenous production to obtain a therapeutic effect. Oxidized glutathione with or without extenders are used in drug forms.

Abstract: The present invention provides peptides and peptidomimetics corresponding to part or to the entirety of the region encompassed by residues 360-386 of human p53, said peptides and peptidomimetics characterized by the ability to activate DNA binding of wild-type p53 and to select tumor-derived p53 mutants. Pharmaceutical compositions of the compounds of the invention and methods of using these compositions therapeutically are also provided.

Abstract: The present invention relates to a linker shown by the following formula (I): X—SO2—R1—(A)m—R2  (I) wherein R1 is a group of the formula (A): [wherein R3, R4 and R5 are the same or different hydrogen, etc], etc, R2 is a group which can form a chemical bond to a resin which may be protected by a conventional protective group, A is lower alkylene, etc, X is a leaving group, and m is an integer of 0 or 1, with proviso that A is (C2-C6)alkylene, and m is an integer of 1, when R1 is a group of the formula (A).

Abstract: Peptide derivatives which are antagonists of neurokinin A. The derivatives have a modified peptide bond having a reduced amide and a fluorinated alkyl attached to the nitrogen atom of the modified peptide bond. For example, Asp-Ser-Phe-Val-Gly-Leu&PSgr;[CH2N(CH2CF3)]Leu(NH2).

Abstract: A dendritic compound comprises two dendrons, each comprising dendritically linked amino acid units, preferably lysine units, joined to a focal group. One of the dendrons includes terminal branches including anchor groups constituted by hydrophobic units and the second dendron has terminal branches which are linked or may be linked to active ligands or sugar moieties. Methods for synthesising the dendritic compounds using solid phase peptide synthetic techniques including lipidic amino acid reagents is described. The compounds serve as a basis for multiple antigenic peptides or drug delivery systems.

Abstract: The invention concerns pharmacologically useful peptide derivatives of the formula (I): P-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-Q, and pharmaceutically acceptable salts thereof, wherein either AA3 together with AA4, or AA4 together with AA5, or AA6 together with AA7 form a group of formula (II): in which Ra is selected from hydrogen and (1-4C)alkyl, and the remainder of AA1, AA2, AA3, AA4, AA5, AA6, AA7, and AA8 are L-amino acid residues; P is a hydrophobic residue; and Q is OH, NH2 or NRcRd. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds, and pharmaceutical compositions containing them, in treating MHC class II dependent T-cell mediated autoimmllne or inflammatory diseases, such as rheumatoid arthritis.

Abstract: The present invention relates to building units suitable for the synthesis of backbone cyclized peptides. The building units of this invention have structures of Formula (I): X—AAm—U—AAp—Y  (I) wherein AAm and AAp are residues of natural or synthetic amino acids and U is C&agr;ON[(CH2)n+1W] or &PSgr;(C&agr;H2N)[CO(CH2)qW], in which C&agr; is a carbon atom and is the &agr; carbon of AAm if m>0. W is NH—X or COY, and X is H, Boc, Z, Fmoc, or Alloc while Y is the hydroxyl group of a carboxylic acid moiety or a carboxylic acid protecting group. The letter m refers to an integer from 0 to 10; n is a number from 0 to 6; p is a number from 1 to 10; and q is a number from 1 to 6. The present invention is also directed to methods of synthesizing building units of Formula (I) via different routes.

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: Provided are methods of inhibiting the activity of a serine protease using protease inhibitors that include an alpha-keto heterocycle in their structure. The methods are useful in the treatment of ischemic heart or treatment of symptoms associated with blood coagulation disorders. Also provided are methods for detecting or quantifying the activity of a serine protease in a pure sample.

Abstract: LH-RH analogues with excellent affinity for LH-RH receptors, of the formula A.sub.1 -A.sub.2 -W-A.sub.3 -A.sub.4 -SPL-A.sub.5 -A.sub.6 -Pro-Z(I) in which:-A.sub.1 is pGlu, AcSar or an aromatic D-amino acid;-A.sub.2 is a direct bond, His, DPhe, DpFPhe or DpClPhe;*W is an aromatic L- or D-amino acid;-A.sub.3 is Ala, Thr, Ser, DSer, Ser(OBzl) or MeSer;-A.sub.4 is Tyr, Phe, cPzACAla, L- or D-PicLys, L- or D-NicLys or L- or D-IprLys;*SPL is the spirolactam of formula: ##STR1## -A.sub.5 is an amino acid with a (C.sub.1 -C.sub.8)alkyl or (C.sub.3-C.sub.6)cycloalkyl side chain;-A.sub.6 is L- or D-(Arg, HArg, Lys, HLys, Orn, Cit, HCit or Aph), where L- or D-(Arg and HArg) can be substituted by one or two (C.sub.1 -C.sub.4)alkyl groups and L- or D-(Lys, HLys, Orn and Aph) can be substituted by an isopropyl, nicotinoyl or picolinoyl group; and*Z is GlyNH.sub.2, DAlaNH.sub.2, AzaGlyNH.sub.2 or --NHR.sub.1 where R.sub.1 is a (C.sub.1 -C.sub.

Abstract: The invention is based on new methods for making and using compounds and arrays of novel .alpha.-ketoamides, and the arrays and compounds made by these methods. These novel compounds are potential inhibitors of proteolytic enzymes, particularly cysteine proteases such as cruzain. Application of the new methods has led to the identification of a number of new inhibitors, from amongst an array of about 38,000 .alpha.-ketoamide derivatives, having specific activity against three cysteine proteases: cruzain, papain, and cathepsin B. These compounds and other compounds identified by the methods described herein can be useful, for example, in developing pharmaceutic agents for the treatment of diseases (e.g., Chagas' disease) associated with these proteases. Although the disclosed compounds have specific activity for cruzain, papain, cathepsin B, the methods described herein can also be used to identify inhibitors of other proteases.

Abstract: This invention is directed to peptide inhibitors of serine proteases, espcecially thrombin, in which the P1-P2 natural amide linkage is replaced by another bond. Exemplary thrombin inhibitors have the formula: X-(aa.sup.3)-(aa.sup.2)-.psi.-(aa.sup.1)-Z wherein X is H or a substituent on the N-terminal amino group, aa.sup.3 is a hydrophobic amino acid, aa.sup.23 is Pro, aa.sup.1 is Arg or an Arg analgoue, Z is --COOH or a heteroatom acid group and .psi. is a non-amide linkage.

Abstract: PNA synthesis using a base-labile amino protecting group Processes are described for preparing PNA oligomers, ##STR1## in which R.sup.0 is hydrogen, alkanoyl, alkoxycarbonyl, cycloalkanoyl, aroyl, heteroaroyl, or a group which favors the intracellular uptake of the oligomer, A and Q are amino acid residues, k and 1 are 0 to 20, n is 1-50, B is a nucleotide base which is customary in nucleotide chemistry, and Q.sup.0 is OH, NH.sub.2, or alkylamino which can be substituted by OH or NH.sub.2. In these processes, the amino acid residues and the structural components ##STR2## in which PG is a base-labile amino protecting group and B' is a nucleotide base which is protected on its exocyclic amino function, are coupled step-wise, in accordance with the solid-phase method, onto a polymeric support which is provided with an anchor group, and, after the construction is complete, the target compounds are cleaved from the polymeric support using a cleaving reagent.

Abstract: Compounds of the invention inhibit urokinase plasminogen activator or uPAR: ##STR1## where R.sub.10 is --CH(R.sub.9)XCH(R.sub.1)(R.sub.11) or a capping group, where X is NR.sub.12, CR.sub.12 R.sub.15, O, S, SR.sub.12, or SR.sub.12 R.sub.15 ; R.sub.1, R.sub.9, R.sub.11, R.sub.12 R.sub.15 are each H, lower alkyl, lower alkenyl, lower alkynyl, aryl, aralkyl, aryl-alkenyl, aryl-alkynyl, aryl-cycloalkyl, substituted with 0-3 halo, OH, NH.sub.2, lower alkyl, halo-lower alkyl, lower alkoxy, lower alkylamino, lower alkylthio, CN or NO.sub.2 ; R.sub.16 is --CH(R.sub.5)C(.dbd.O)NH.sub.2, H, lower alkyl, cycloalkyl, or lower alkenyl; 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 and R.sub.5 are each independently H or lower alkyl; R.sub.4 is --CH.sub.2 C(.dbd.O)NR.sub.13 R.sub.14, where R.sub.13 is H, lower alkyl, phenyl or benzyl, and R.sub.

Abstract: .beta.-sheet mimetics and methods relating to the same are disclosed. The .beta.-sheet mimetics have utility as protease and kinase inhibitors, as well as inhibitors of transcription factors and protein-protein binding interactions. Methods of the invention include administration of a .beta.-sheet mimetic, or use of the same for the manufacture of a medicament for treatment of a variety of conditions associated with the targeted protease, kinase, transcription factor and/or protein-protein binding interaction.

Abstract: Novel homodimers that include cysteine-containing peptides having 4-15 amino acid residues can be administered to modulate the immune response in an animal.

Abstract: Peptides synthesized to match the human .alpha.1(II) carboxy-telopeptide sequences of type II collagen degradation products in body fluids, preferably Glu-Lys-Gly-Pro-Asp-Pro (SEQ ID NO:6). Useful as calibrators and antigens in immunoassays for detecting type II collagen degradation products in body fluids.

Abstract: A chemical complex comprising divalent metal ions, preferably Ca.sup.+2 ions, and peptide-peptoid trimers in a fixed ratio and having a centrosymmetric crystalline structure wherein three divalent metal ions at the interior of the complex are coordinated with the peptide carboxylate and urethane oxygen atoms. The globular complex has a hydrophobic outer surface and is useful as an ionophore.

Abstract: The invention concerns pharmaceutically useful peptide derivatives of the formula (I): P--R.sup.1 --R.sup.2 --R.sup.3 --R.sup.4, in which P, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 have the various meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell mediated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.

Abstract: Peptoids are provided which are polymers comprised of monomer units wherein the monomer units include at least some substitute amino acids and may include conventional amino acids. The peptoids can be synthesized in large numbers so as to provide libraries of peptoids which can be screened in order to isolate peptoids of desired biological activity. Although the peptoids may include amino acids, they preferably include only substituted amino acids and are designed in a manner so as to have a particular biological activity. Certain peptoids are designed to mimic as closely as possible the activity of known proteins. Other peptoids are designed so as to have greater or lesser activity than known proteins and may be designed so as to block known receptor sites and/or elicit a desired immunogenic response and thereby act as vaccines. In that the peptoids are comprised of substitute amino acids they can be designed to have structures which natural proteins cannot conform to.

Abstract: A thrombin inhibitor comprising a first bulky hydrophobic portion interacting with the catalytic site of thrombin responsible for proteolysis and a second portion at least maintaining the hydrophobic and acidic character of amino acids 55 to 60 of native hirudin at the C-terminal non-catalytic region of N-acetyl-hirudin45-65. Between the first and second portions is a divalent linker moiety having a chain length of at least 10 carbon atoms. Connecting the first bulky hydrophobic portion and the linker is a peptidomimetic bond. Preferably, the bulky hydrophobic portion comprises at least one amino acid of D-configuration. The compounds are useful in the treatment of thrombotic disorders.

Abstract: Disclosed are .beta.-peptides containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the .alpha. and .beta. carbons of the peptide backbone. The .beta.-peptides adopt stable helical and sheet structures in both the solid state and in solution. Method of generating combinatorial libraries of peptides containing .beta.-peptide residues and the libraries formed thereby are disclosed.

Abstract: A propenamide derivative of the formula (I) having, as an essential structural unit, an adhesive peptide represented by the formula (II) in the side chain or salts thereof:Formula (I): R.sup.1 R.sup.2 C.dbd.CR.sup.3 --CO--[NH]--Formula (II): --[R.sup.4 ]--[CO]--([X]-Arg-Gly-Asp-[Y]).sub.n -[Z]--[R.sup.5 ]--wherein R.sup.1 and R.sup.2 each represents a hydrogen atom or a carboxyl group and R.sup.3 represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group; X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; z represents --O-- or --NH--; one of R.sup.4 and R.sup.

Abstract: The present invention relates to certain substituted oxadiazole, thiadiazole and triazole peptoids which are useful as inhibitors of serine proteases including human neutrophil elastase, equivalently known as human leukocyte elastase.

Abstract: Methods of adjusting or maintaining the intracellular levels of glutathione of a subject are provided. The subject is treated by administering an effective amount of an acetyl derivative of glutathione.

Abstract: Novel microbial peptides called clavanins are of the formulaX'.sub.1 X.sub.2 B'.sub.3 X.sub.4 X.sub.5 U.sub.6 B.sub.7 X.sub.8 X.sub.9 B.sub.10 B.sub.11 X.sub.12 U.sub.13 Z.sub.14 X.sub.15 X.sub.16 B*.sub.17 U.sub.18 X.sub.19 U.sub.20 B.sub.21 X.sub.22 X.sub.23 ( 1)(SEQ ID NO: 1)including the salts, esters, amides and acylated forms thereofwherein X is a hydrophobic amino acid residue or modified form thereof;X' is a small or a hydrophobic amino acid residue or a modified form thereof;B is a basic amino acid residue or modified form thereof;B' is basic or a polar/large amino acid residue or modified form thereof; andB* is a basic or a hydrophobic amino acid residue or a modified form thereof;U is a small amino acid residue or modified form thereof;Z is a polar/large amino acid residue or modified form thereof.

Abstract: Novel microbial peptides called clavaspirins are of the formula (SEQ ID NO:1)X'.sub.1 X.sub.2 B'.sub.3 X.sub.4 X.sub.5 U.sub.6 U.sub.7 X.sub.8 X.sub.9 B.sub.10 X'.sub.11 X.sub.12 U.sub.13 B.sub.14 X.sub.15 X.sub.16 B*.sub.17 B.sub.18 X.sub.19 U.sub.20 X.sub.21 X'.sub.22 X.sub.23 (1)including the salts, esters, amides and acylated forms thereofwherein X is a hydrophobic amino acid residue or modified form thereof;X' is a small or a hydrophobic amino acid residue or a modified form thereof;B is a basic amino acid residue or modified form thereof;B' is basic or a polar/large amino acid residue or modified form thereof;B* is a basic or a hydrophobic amino acid residue or a modified form thereof; andU is a small amino acid residue or modified form thereof.

Abstract: An inhibitor of the HCV NS3 protease. The inhibitor is a subsequence of a substrate of the NS3 protease or a subsequence of the NS4A cofactor. Another inhibitor of the present invention contains a subsequence of a substrate linked to a subsequences of the NS4A cofactor. In another embodiment the inhibitor is a bivalent inhibitor comprised of a subsequence, a mutated subsequence or a mutated full-length of a substrate of the NS3 protease linked to a subsequence, a mutated subsequence or a mutated full-length suquence of the HCV NS4A cofactor.

Abstract: This invention relates to diagnostic and radiodiagnostic agents, including radiolabeled scintigraphic imaging agents, and therapeutic and radiotherapeutic agents. The invention provides such agents and reagents for preparing such agents, and methods for producing and using such reagents. Specifically, the invention provides radiolabeled imaging agents and non-radioactively labeled imaging agents for imaging sites in a mammalian body and reagents for preparing these imaging agents. The invention also provides radiolabeled therapeutic agents, as well as non-radioactively labeled therapeutic agents, and reagents and methods for preparing these agents. The agents and reagents provided comprise a specific binding peptide, covalently linked to a metal ion-complexing moiety. Reagents, methods and kits for making such reagents, methods for labeling such reagents, and methods for using such labeled reagents are provided.

Abstract: The use of a) an angiotensin-converting enzyme (ACE) inhibitor such as Captopril or Enalapril, b) an angiotensin II-receptor antagonist such as Saralasin or Losartan, or c) a renin inhibitor, such as Remikiren or [N-(pyridyl-3-propionyl)-phenylalanyl-histidyl-(3S,4S) ACHPA-isoleucylamino]-2-methyl-2-dihydroxy-1,3-propane, for the manufacture of a medicament for the treatment of uterine fibroids is disclosed. The ACE inhibitor may be used concomitantly or sequentially with a gonadotropin-releasing hormone agonist such as Buserelin or Goserelin.

Abstract: Peptoids are provided which are polymers comprised of monomer units wherein the monomer units include least some substitute amino acids and may include conventional amino acids. The peptoids can be synthesized in large numbers so as to provide libraries of peptoids which can be screened in order to isolate peptoids of desired biological activity. Although the peptoids may include amino acids, they preferably include only substituted amino acids and are designed in a manner so as to have a particular biological activity. Certain peptoids are designed to mimic as closely as possible the activity of known proteins. Other peptoids are designed so as to have greater or lesser activity than known proteins and may be designed so as to block known receptor sites and/or elicit a desired immunogenic response and thereby act as vaccines. In that the peptoids are comprised of substitute amino acids they can be designed to have structures which natural proteins cannot conform to.

Abstract: Antigens capable of eliciting antibodies which can catalyze chemical reactions, in particular, the cleavage or formation of a peptide linkage, comprising a hapten or a hapten and a suitable carrier molecule are disclosed. Haptens include, among others, silicon and boron containing compounds. Antibodies which are catalytically active for chemical reactions, in particular, the cleavage or formation of a selected peptide linkage or an ester bond, and which are elicited by such antigens are disclosed as well as methods for producing the antibodies and methods for catalyzing the cleavage or formation of a peptide linkage or in ester bond in a molecule.

Abstract: The present invention relates a number of different lysine containing peptides which can be administered to a mammal to normalize cardiac pressure for treatment of heart disease conditions such as myocardial ischemia. These peptides include certain known peptides, some of which are capable of liberating growth hormone to various degrees when administered to a mammal. Other peptides useful in the invention are novel peptide sequences which include a spirolactam, bicyclic or tricyclic peptidomimetic unit. The peptides disclosed herein exhibit binding to cardiac tissue and normalize cardiac pressure after administration, thus imparting cardiac protecting activity by a mechanism which at the present is unknown. One common feature of the peptides of this invention is that at least one lysine unit is present.

Abstract: D-enzyme compositions are described comprising an amino acid residue sequence that defines an polypeptide able to catalyze an enzymatic reaction. The D-enzyme has an amino acid residue sequence consisting essentially of D-amino acids.

Abstract: Compounds of the formula ##STR1## or of the formula ##STR2## or the amides, esters or salts thereof, wherein: S.sup.x is S.dbd.O, O.dbd.S.dbd.O, S.dbd.NH, HN.dbd.S.dbd.O, Se.dbd.O, O.dbd.Se.dbd.O, Se.dbd.NH, HN.dbd.Se.dbd.O, S.sup.+ R.sup.3 wherein R.sup.3 is alkyl (1-6C) or O--C.dbd.O or HN--C.dbd.O;each R of R.sup.1, and R.sup.2 is independently H or a noninterfering substituent;wherein (conj) represents a conjugated system capable of transmitting electrons;n is 0 or 1;YCO is selected from the group consisting of .gamma.-Glu, .gamma.-Glu-Gly, Glu, Glu-Gly, .beta.Asp, .beta.-Asp-Gly, Asp and Asp-Gly;AA.sub.C is an amino acid linked through a peptide bond to the remainder of said compound of Formula 1; andN(Z) represents a reduced nitrogen-containing leaving group and L represents an electron-withdrawing leaving group,are useful as prodrugs and to generate active components released by the activity of glutathione S-transferase.

Abstract: Disclosed herein are template assembled synthetic protein (TASP) molecules that contain dendritic linkage units having the structure .psi. (CO--S--CH.sub.2 --CO--NH). Also disclosed are methods of preparing the template assembled synthetic proteins.

Abstract: This invention relates to peptide derivatives, pharmaceutical formulations containing those compound and methods of their use as thrombin inhibitors.

Abstract: A plasmin solution, comprising:(A) plasmin, and (B) the following component (B-1), (B-2) or (B-3):(B-1) an oligopeptide comprising at least two amino acids bonded to each other, where the two amino acids are selected from the group consisting of lysine, arginine, glycine, alanine, aspartic acid and methionine;(B-2) at least two amino acids selected from the group consisting of lysine, arginine, glycine, alanine, aspartic acid and methionine; or(B-3) an amino acid selected from the group consisting of lysine, arginine, glycine, alanine, aspartic acid and methionine, and a polyhydric alcohol. This solution is stable, maintains plasmin activity even after long-term storage, and can be used as a reagent for quantitatively measuring .alpha.2PI.

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: Process for the preparation of modified proteins comprising the coupling of a first peptide segment having a haloacyl group at the N-terminus thereof with a second peptide segment having a carbonylthiol group at the C-terminus thereof are disclosed. Novel modified proteins produced by the process are also disclosed.