Abstract: The present invention relates to a new process for the preparation of substituted aryllactic acid-containing cyclodepsipeptides having 24 ring atoms of the formula (I): ##STR1## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4 have the meaning given in the description,with the aid of fungal strains of the species Agonomycetales or enzymatic preparations isolated therefrom.

Abstract: A peptide of the formula (I): X.sup.1 -A.sup.1 -A.sup.2 -X.sup.2 -Asn-X.sup.3 -X.sup.4 -P.Tyr-X.sup.5 -X.sup.6 -X.sup.7 -X.sup.8, wherein X.sup.1 represents Lys, Arg, His, Ser, Thr, Tyr, Asn, Leu, Val or Glu, A.sup.1 represents Trp, Leu, Ala, Ser, Ile, Glu, Met, Gly, Cys, Phe, Pro or Val, and A.sup.2 represents Ala, Val, Leu, Ile, Ser, Met, Phe, Gly, Cys, Trp or Pro, X.sup.2 represents Glu, Asn, Tyr, Thr, Ser, Asp or Ile, X.sup.3 represents Pro, Met, Trp, Phe, Ala, Lys, Val, Leu, Ile, Gly or Ser, X.sup.6 represents Ser, Thr, Tyr, Asn, Glu, Met, Ala, Leu, Val or Gly, X.sup.7 represents Asp, Glu, Ala, Val, Leu, Ile, Gly, Cys, Phe, Trp, Met, Pro, Ser or Asn and X.sup.8 which may be present or absent represents Phe, Trp, Pro, Leu, Ala, Val, Ile, Gly, Cys, Met, Asp, Ser or Arg which interferes with the interaction of a PTB domain containing protein with a PTB domain binding site, and truncations and analogues of the peptide.

Abstract: Z domain variants of staphylococcal protein A have significantly reduced size but possess IgG-binding affinity equivalent to the wild type Z domain. These Z domain variants are suitable for use in affinity chromatography purification of proteins and in the treatment of staphylococcic diseases.

Abstract: Kalahide F. of formula I below, may be isolated from a secoglossan. The compound may be used in the manufacture of pharmaceutical compositions or in the treatment of tumors or viral conditions.

Abstract: Cyclosporin derivatives of formula (I) in which R is H or a radical (Ia) or (Ib) as defined herein; R' is a radical (Ic) or (Id) as defined herein; and R"represents H or OH, with the proviso that R and R" are not simultaneously H, and pharmaceutically acceptable salts thereof, when they exist, are disclosed as useful for the treatment and/or prophylaxis of retrovirus infections.

Abstract: The present invention relates to methods of treating or preventing diseases or disorders associated with hematopoietic deficiency by administration of human chorionic gonadotropin, .beta.-human chorionic gonadotropin or a peptide containing a sequence of a portion of .beta.-human chorionic gonadotropin. The invention also relates to methods of treating or preventing diseases or disorders associated with hematopoietic deficiency by administration of hematopoietic cells, the numbers of which have been increased by contacting the cells with human chorionic gonadotropin, .beta.-human chorionic gonadotropin or a peptide containing a sequence of a portion of .beta.-human chorionic gonadotropin. The invention also provides assays for the utility of particular human chorionic gonadotropin preparations in the treatment or prevention of hematopoietic deficiencies or in the increasing of hematopoietic cell numbers in vitro. Pharmaceutical compositions and methods of administration of are also provided.

Abstract: The present invention provides novel macrocyclic difluorostatone derivatives which are useful as antiviral agents. More specifically, these novel compounds are useful as inhibitors of retroviral proteases required for replication, particularly the HIV-1 and HIV-2 viral proteases, in the prevention or treatment of infection by the human immunodeficiency virus (HIV), and in the treatment of consequent pathological conditions such as the acquired immunodeficiency syndrome (AIDS) in mammals capable of being infected with HIV virus.

Abstract: Cyclic pentapeptides are disclosed having the following formula (I) --Cyclo(-A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 -A.sub.5 -)-- wherein A.sub.1, A.sub.2, A.sub.3, A.sub.4 and A.sub.5, are amino acid residues. The pentapeptide has amino acid residues in positions 1-2-3 to form a .gamma.-turn, and amino acid residues in positions 3-4-5-1 to form a .beta.-turn in combination with the .gamma.-turn. D-.alpha.-amino acid residues are selected for A.sub.1, A.sub.3, and A.sub.5 and L-.alpha.-amino acid residues are selected for A.sub.2 and A.sub.4. Compounds having .gamma.-turns and .beta.-turns can be synthesized, regardless of the kinds of amino acid residues, and it is possible to synthesize compounds in which desired amino acid residues are introduced into sites of .beta.-turn and .gamma.-turn based on their importance from the viewpoint of biological activity. The present invention is therefore available for design of compounds having biological activity.

Abstract: Methods for obtaining beneficial stable levels of circulating histamine are disclosed for use in methods for enhancing natural killer cell cytotoxicity. In such methods, a beneficial level of circulating histamine is attained and an agent whose ability to enhance natural killer cell cytotoxicity is augmented by histamine is administered. Alternatively, stable beneficial levels of circulating histamine can be attained in subjects receiving chemotherapy or antiviral treatment. The invention may also be employed in treatments combining histamine, agents which enhance natural killer cell cytotoxicity, and chemotherapeutic agents.

Abstract: The cyclosporin compound of formula (I) is particularly useful in the treatment and/or prophylaxis of retrovirus infections.

Abstract: The invention refer to a method for diagnosing the presence of infection of papilloma virus (PV) and of papilloma virus (PV) carrying, especially cervix cancer and condyloma, by the detection of virus specific antigen-antibody complexes in immunossay.

Abstract: Salinamides A and B are disclosed. These two bicyclic depsipeptides are produced by fermentation of a specific marine actinomycete, a Streptomyces sp, (CNB-091) in saltwater-based media. Salinamides A and B are useful as anti-biotic and anti-inflammatory agents.

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: Disclosed are (1) a cyclic hexapeptide represented by formula I or a salt thereof: ##STR1## wherein X and Y each represent .alpha.-amino acid residues, A represents a D-acidic-.alpha.-amino acid residue, B represents a neutral-.alpha.-amino acid residue, C represents an L-.alpha.-amino acid residue and D represents a D-.alpha.-amino acid residue having an aromatic ring group; and (2) a pharmaceutical composition comprising the peptide represented by formula I or a pharmaceutically aceptable salt thereof as an active ingredient.

Abstract: A process for the isolation of cyclosporin A comprising the steps of: adding a lower alkanol solvent to a culture fluid of a mutant of Tolypocladium inflatum to form a mixture, filtering the mixture to form an extract, transferring the extract to methylene chloride as a solvent therefor, and column chromatographing the resultant product on silica gel.

Abstract: The present invention is directed to novel 38-decarboxy-38-hydroxymethyl derivatives of teicoplanin antiobiotics and a process for preparing them which includes submitted the corresponding lower alkyl ester precursor to a reduction reaction in the presence of an alkali metal borohydride. The compounds of the invention show an improved antibacterial activity against some clinical isolates of Staphylococci somewhat resistant to teicoplanin.The teicoplanin derivatives of the present invention are represented by the following formula: ##STR1## wherein: X represents hydroxymethyl;R represents hydrogen or --N?(C.sub.9 -C.sub.12)aliphatic acyl!-.beta.-D-2-deoxy-2-aminoglucopyranosyl;R.sub.1 represents hydrogen or N-acetyl-.beta.-D-2-deoxy-2-aminoglucopyranosyl;R.sub.2 represents hydrogen of alpha-D-mannopyranosyl;R.sub.3 represents hydrogen or a protecting group of the amino function; and the acid addition salts thereof; with the proviso that R.sub.1 represents hydrogen only when R and R.sub.

Abstract: The invention relates to compounds of the formula Icyclo(A-B-C-E-F-(D)-Ala) (I)in whichA, B, C, E and F are each independently the residue of a natural amino acid other than cysteine (Cys) and tryptophan (Trp), their mixtures and their physiologically tolerated salts; to a process for their preparation and to their use for preparing a diagnostic agent, a medicament for the treatment or prophylaxis of allergies and infections, or a scientific tool for inhibiting the binding of interleukin-4 (IL-4) to the IL-4 receptor.

Abstract: The present invention provides novel cyclic tetrapeptides useful in the treatment or prevention of protozoal diseases; in particular, the novel compounds are active against the causative pathogens in malaria, toxoplasmosis, and coccidiosis.

Abstract: The present invention relates to a process for making a highly productive fusant of Tolypocladium inflatum, a producing strain of cyclosporin A with immunosuppressive properties wherein the selection of the fusant KD461, designed to produce a large amount of cyclosporin A, was made available by the following steps of: developing amino acid-dependent mutants of Tolypocladium inflatum, wild strain isolated from soil, which mutants are induced by UV radiation; conjugating L-valine-dependent and L-leucine-dependent mutants to promote the demand and utility of L-valine and L-leucine, precursors of cyclosporin A, together with an organic nitrogen-source.

Abstract: A method of producing analgesia in nociceptive and neuropathic pain is disclosed. The method includes administering to a subject an omega conopeptide which is characterized by its ability to (a) inhibit electrically stimulated contraction of the guinea pig ileum, and (b) bind selectively to omega conopeptide MVIIA binding sites present in neuronal tissue. Also disclosed are novel omega conotoxin peptides effective in producing analgesia.

Abstract: Compounds are provided which are crossreactive with peptides such as those which bind G-protein-linked receptors, together with preparative and therapeutic methods therefor.

Abstract: Pharmaceutical compositions comprising a cyclosoporin, e.g. Ciclosporin, and a mono- or poly-unsaturated fatty acid or alcohol, e.g. oleic acid or oleyl alcohol. The compositions are suitable for dermal application, e.g. in the treatment of autoimmune disease of the skin or for the promotion of hair growth.

Abstract: A cyclic depsipeptide having the general formula (I) ##STR1## (wherein n is an integer of 5-15) or a pharmacologically acceptable salt thereof. The present compound can be prepared by cultivation of a cyclic depsipeptide-producing microorganism belonging to the genus of Bacillus. The present compounds are useful as a therapeutic agent for hyperlipemia, an agent for inhibiting the secretion of lipids or an agent for inhibiting the production of apolipoprotein B.

Abstract: A novel, cyclosporin-producing microbe is described. A process for the production of cyclosporin, comprising culturing the novel microbe and recovering the desired form of cyclosporin produced, is described.

Abstract: The present invention is directed to novel antibiotic A 40926 derivatives characterized by having a carboxy, (C.sub.1 -C.sub.4) alkoxy-carbonyl, aminocarbonyl, (C.sub.1 -C.sub.4) alkylaminocarbonyl, di (C.sub.4 -C.sub.4)alkylaminocarbonyl or hydroxymethyl substituent on the N-acylaminoglucuronyl moiety and a hydroxy or a polyamine substituent in position 63 of the molecule. The compounds of the invention show high in vitro activity against glycopeptide resistant Enterococci and Staphylococci.

Abstract: A novel, cyclosporin-producing microbe is described. A process for the production of cyclosporin, comprising culturing the novel microbe and recovering the desired form of cyclosporin produced, is described.

Abstract: The present invention provides novel peptides having as their core region portions of the 109-118 amino acid sequence of P-selectin, E-selectin or L-selectin. The invention also provides pharmaceutical compositions comprising the peptides of the invention, and diagnostic and therapeutic methods utilizing the peptides and pharmaceutical compositions of the invention.

Abstract: The present invention provides a method for isolating cyclosporin by adsorption chromatography. The method comprises the steps of: (a) loading a crude solution containing a cyclosporin onto adsorption chromatography column containing an adsorption resin, (b) eluting the cyclosporin from the adsorption chromatography column, and (c) collecting the eluted cyclosporin. The step of eluting the cyclosporin is carried out by passing an eluting solvent through the column, which comprises a hydrophilic component and a lipophilic component, wherein the cyclosporin is separately eluted from other compounds by providing a hydrophilic/lipophilic balance in the eluting solvent that selectively desorbs the cyclosporin from the column.

Abstract: Peptide-based compounds containing four invariant cysteine residues which have been optionally oxidized to contain two intramolecular disulfide bonds, or modified forms where the cysteines are replaced, are useful as preservatives and in preventing, treating, or ameliorating viral or microbial infection in animals and plants, and in inactivating endotoxin. These compounds, in one embodiment, are of the formula:A.sub.1 -A.sub.2 -A.sub.3 -A.sub.4 -A.sub.5 -C-A.sub.7 -C-A.sub.9 -A.sub.10 -A.sub.11 -A.sub.12 -C-A.sub.14 -C-A.sub.16 -(A.sub.17 -A.sub.18)(1)(SEQ ID NO:1)and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, either in optionally --SH stabilized linear or in cystine-bridged formwherein A.sub.1, A.sub.9, A.sub.10, and A.sub.11 are basic amino acids;A.sub.2 and A.sub.3 are small amino acids;A.sub.5, A.sub.7, A.sub.12, A.sub.14 and A.sub.16 are hydrophobic amino acids; andA.sub.4 is a basic or a small amino acid;A.sub.

Abstract: Salinamides A and B are disclosed. These two bicyclic depsipeptides are produced by fermentation of a specific marine actinomycete, a Streptomyces sp, (CNB-091) in saltwater-based media. Salinamides A and B are useful as anti-biotic and anti-inflammatory agents.

Abstract: A new peptide, .kappa.-conotoxin PVIIA, is disclosed. This peptide is found naturally in the cone snail Conus purpurascens and has the amino acid sequence Cys-Arg-Ile-Xaa-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-Cys-Ser-Arg-Ly s-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val (SEQ ID NO:1) where Xaa represents 4-trans-hydroxyproline hydroxyproline or proline. This peptide together with a previously disclosed peptide, .delta.-conotoxin PVIA, act synergistically to rapidly immobilize fish which are injected with the two peptides. Injection of .kappa.-conotoxin PVIIA alone results in different symptoms with an injected fish becoming hyperactive and then contracting and suddenly extending all major fins. This "fin-popping" occurs repeatedly resulting in a series of jerky movements, but injection of only .kappa.-conotoxin PVIIA does not immobilize or kill the fish.

Abstract: This application discloses seven newly synthesized pentapeptide amides and our tetrapeptide amides. The synthesis utilized both naturally occurring and modified amino acids; the modified amino acids are constituents of the well known dolastatin 10 and dolastatin 15 which are structurally distinct peptides with excellent antineoplastic activity. These peptides were constructed by introducing a peptide bond between selected amino acids and modified amino acids and coupling the resulting di- and tri-peptides to obtain peptides having a high anticancer activity against a series of human cancer cell lines.

Abstract: Novel compounds of the general composition I, Lactate (1), Glycine (1), Valine (4), Isoleucine (1), pipecolic acid (1), Aspartic acid (1), Tyrosine (1), wherein each amino acid residue independently may occur in L- or D- form, and wherein the number in parenthesis indicates the number of occurrences of each moiety, and derivatives thereof are disclosed. The compounds are producible by aerobic cultivation on suitable nutrient media under suitable conditions of a strain of the fungus Curvularia sp., subsequent recovery of the active component from the fermentation medium, and optionally modifying the active compound to obtain a compound of the desired general composition. Disclosed are also microorganisms capable of producing said compounds, compositions containing said compounds, and the use of such compositions for controlling fungi in crops, and in the preservation of wood, paints, cosmetics, and edible products.

Abstract: The cytostatic, cyclic peptides; phakellistatin 4, phakellistatin 5, phakellistatin 6, phakellistatin 7, phakellistatin 8 and phakellistatin 9 were isolated from the Western Pacific Ocean sponge Phakellia costata. Structural determination was accomplished by utilizing high-field, 2D-NMR experiments and confirmed by results of FAB-MS/MS studies. The absolute configurations were deduced by analyzing the acid hydrolysates using chiral gas chromatographic analytical techniques. The new cyclic peptides were found to have significant in vitro P388 ED.sub.50 values which range between 0.18 .mu.g/ml and 4.1 .mu.g/ml.

Abstract: Fungicidal compositions comprising compounds of the general formula III ##STR1## cyclo-[Pec-MeAsp-MeVal-Val-MeVal-MeIle-Gly-MeVal-TyrOMe-D-Lact] (III) wherein each amino acid residue and the lactate residue independently may occur in L- or D-form, and derivatives thereof in combination with other biocidal agents are disclosed. Said compositions may be used for controlling fungi in crops and in the preservation of wood, paints, cosmetics, and edible products.

Abstract: The present invention is concerned with tetrahydronaphthalene derivatives which are mimics of domains of peptides or proteins which can interact with other proteins or with DNA or RNA through .alpha.-helical conformation, said tetrahydronaphthalene derivatives having the formulae: ##STR1## are valuable aids in the determination of biologically active peptide sequences and are accordingly so-called "research tools". They are, however, also potentially suitable as medicaments.

Abstract: Compositions and methods are described for the synthesis of novel analogs of cyclosporin A, and the use of those analogs as immunostimulatory agents.

Abstract: Peptide-based compounds containing six invariant cysteine residues are useful as preservatives and in preventing, treating, or ameliorating microbial infection in animals and plants. These compounds are of the formulas: ##STR1## wherein each B.sub.i is a basic amino acid and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, either in optionally --SH stabilized linear or in cystine-bridged form.

Abstract: Novel compounds of the general composition I, Lactate (1), Glycine (1), Valine (1), Isoleucine (1), pipecolic acid (1), Aspanic acid (1), Tyrosine (1), wherein each amino acid residue independently may occur in L- or D- form, and wherein the number in parenthesis indicates the number of occurrences of each moiety, and derivatives thereof are disclosed. The compounds are producible by aerobic cultivation on suitable nutrient media under suitable conditions of a strain of the fungus Culvularia sp., subsequent recovery of the active component from the fermentation medium, and optionally modifying the active compound to obtain a compound of the desired general composition. Disclosed are also microorganisms capable of producing said compounds, compositions containing said compounds, and the use of such compositions for controlling fungi in crops, and in the preservation of wood, paints, cosmetics, and edible products.

Abstract: The present invention provides novel cyclic tetrapeptides useful in the treatment or prevention of protozoal diseases; in particular, the novel compounds are active against the causative pathogens in malaria, toxoplasmosis, and coccidiosis.

Abstract: Lipophilic and amphiphilic therapeutic or diagnostic agents having water solubilizing groups attached thereto by bonds that can be cleaved readily by one or more of the various proteases that are active in the extracellular fluid or on the surfaces of cells in many types of malignant tissue may accumulate selectively in such malignant tissues. Protease mediated removal of the water solubilizing groups converts such drugs into lipophilic or amphiphilic forms which are more soluble in plasma membrane lipids and which therefore enter cells more readily. Since the extracellular fluid in most non-malignant tissues under normal circumstances has little such protease activity, removal of the water solubilizing groups takes place primarily within malignant tissues, with consequent preferential accumulation of the lipophilic or amphiphilic forms of the drug within malignant tissues.

Abstract: Cyclic peptides and their salts have antagonistic activity on endothelin receptors and antagonistic activity on NK2 receptors. The peptides have the formula ##STR1## wherein X and Y each represent .alpha.-amino acid residues, A represents a D-acidic-.alpha.-amino acid residue, B represents a neutral .alpha.-amino acid residue, C represents an L-.alpha.-amino acid residue and D represents a D-.alpha.-amino acid residue having an aromatic ring group; wherein hydroxy, thiol, amino, imino and carboxyl groups can be substituted or unsubstituted. Pharmaceutical compositions containing such peptides are also described.

Abstract: A cyclic heptapeptide anti-inflammatory agent named cyclomarin-A is disclosed. Cyclomarin-A is produced by a specific marine actinomycete. The cyclomarin-A producing bacterium is isolated from sediment located in marine estuaries in and around San Diego, Calif. Fermentation of the isolated bacterium in saltwater-based media produces cyclomarin-A as a secondary by-product. The cyclomarin-A is useful as an anti-inflammatory agent.

Abstract: A method of treating a patient with diabetes involving administering to the patient a hybrid molecule which contains a cytotoxin covalently joined to interleukin-2 which is capable of binding to interleukin-2 receptor on a cell that contributes to the disease state of the cell and decreasing the viability of that cell.

Abstract: Centrally truncated NPY cyclic peptide analogs are described which have selective bioactivity for NPY Y1 receptors. Methods are provided for diagnosing physiological disorders manifested by abnormal levels of endogenous Y1 receptors, by means of measuring the amount of a NPY Y1 specific cyclic peptide analog which binds to a biological sample, and by means of administering a radiolabelled NPY Y1 specific cyclic peptide analog to a host subject followed by radiographic imaging. A method is further provided for therapeutic use of the cyclic peptide NPY analogs in clinical treatment of hypotension and anorexia.

Abstract: Technetium or rhenium radionuclide labelled chelate-hexapeptide complexes are useful for the selective detection or treatment of tumors with somatostatin receptors. In particular, compounds of formula: ##STR1## (wherein R, R.sup.1, R.sup.3 and A are as defined herein) incorporating an N3S2 chelate may be labelled with a radionuclide. The resulting complexes are useful as radioimaging agents or as radiopharmaceuticals for the treatment of certain tumors.

Abstract: The present invention relates to a novel polypeptide having the following presumed structure: ##STR1## and the compound has both excellent fungicidal and protozoicidal effects.

Abstract: This application discloses seven newly synthesized pentapeptide amides and our tetrapeptide amides. The synthesis utilized both naturally occurring and modified amino acids; the modified amino acids are constituents of the well known dolastatin 10 and dolastatin 15 which are structurally distinct peptides with excellent antineoplastic activity. These peptides were constructed by introducing a peptide bond between selected amino acids and modified amino acids and coupling the resulting di- and tri-peptides to obtain peptides having a high anticancer activity against a series of human cancer cell lines.

Abstract: Cyclosporins wherein the residue at the 1-position (typically -MeBmt- or -dihydro-MeBmt-) is 3'O-acylated or 3'-oxo or -C.sub.1-4 alkoxyimino substituted, or wherein the residue at the 2-position is .beta.-O-acyl or .beta.-oxo substituted, or wherein the residue at the 2-position is -Ile-, or wherein the residue at the 11-position is -MeAls-, -MeIle- or -MealloIle- as well as various naturally occurring cyclosporins/dihydro-derivatives thereof, are useful in reversing resistance to chemotherapy, in particular resistance to cytostatic or anti-neoplastic therapy. Various of these cyclosporins and intermediates for their production are novel. Intermediates wherein the residue (e.g. -MeBmt-, -dihydro-MeBmt- etc.) at the 1-position is 8'-alkoxy or 7'-desmethyl-7'-hydrocarbyl substituted are novel and useful as immunosuppressants, anti-inflammatory and anti-parasitic agents.

Abstract: The present invention is directed to novel aza cyclohexapeptide compounds of the formula ##STR1## where all substituents are defined herein, which are useful as antifungal agents and for the treatment of Pneumocystis carinii infections. Compositions containing the compounds of the invention are also disclosed.