Abstract: The present invention provides methods of making ?4?7 peptide monomer and dimer antagonists. Methods of the present invention include solid phase and solution phase methods, as well as synthesis via condensation of smaller peptide fragments. Methods of the present invention further include methods directed to the synthesis of peptides comprising one or more penicillamine residues.

Abstract: The invention features echinocandin class compounds. The compounds can be useful for the treatment of fungal infections.

Abstract: The present disclosure provides solid forms of a compound of formula I. In some embodiments, the present disclosure provides crystalline forms of Compound I. In some embodiments, the present disclosure provides solvate forms of Compound I. In some embodiments, the present disclosure provides amorphous Compound I.

Abstract: The invention provides a synthetic polypeptide of Formula I?: or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia.

Abstract: A compound sensitive to and selective for ammonium ions over other ions. A sensor fabricated from a self assembled monolayer of said compound on gold, exhibiting sensitivity and selectivity for ammonium ions over other ions in aqueous solutions, including blood. A method of preparation of said compound and said sensor.

Abstract: The present invention relates to novel cyclic or constrained acyclic compounds which modulate the activity of G protein-coupled receptors and are useful in the treatment of conditions mediated by G protein-coupled receptors, for example, inflammatory conditions.

Abstract: The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain lipopeptide compounds comprising a cyclic peptide bearing a lipid side chain (for convenience, collectively referred to herein as “LP compounds”), which, inter alia, are antimicrobial, particularly antibacterial. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to provide an antimicrobial function, particularly an antibacterial function, and in the treatment of diseases and conditions that are mediated by microbes, particularly bacteria, that are ameliorated by the antimicrobial function, particularly an antibacterial function, including bacterial diseases, optionally in combination with another agent, for example, another antibacterial agent.

Abstract: The present invention is directed to a method of decreasing the rate of proliferation of medullary thyroid carcinoma cells which comprises contacting medullary thyroid carcinoma cells with one or more SSTR2 agonist. A preferred selective somatostatin receptor type-2 (SSTR-2) agonist cyclo[Tic-Tyr-D-Trp-Lys-Abu-Phe] is also disclosed.

Abstract: This invention relates to an improved process for the minimization of acid-catalyzed reactions of certain echinocandins of the kind disclosed in U.S. Pat. No. 5,378,804. The process involves the use of a boronic acid.

Abstract: A subject of the invention, in all possible isomer forms as well as their mixtures, is the compounds of formula (I): in which either R1: H or CH3 and R2: cyclohexyl substituted by an amine, a (CH2)b-C?N radical or R1 and R2 together with the nitrogen which carries them form a ring with 3, 4 or 5 carbons optionally substituted by an amine R3: hydrogen, methyl or hydroxyl R4: hydrogen or hydroxyl R: represents a linear, branched or cyclic chain T: hydrogen, methyl, CH2CONH2, CH2C?N, a (CH2)2NH2 or (CH2)2Nalk+X? radical, X halogen and alk alkyl Y: hydrogen, hydroxyl, halogen or OSO3H, W: H or OH, Z: H, CH3. The compounds of formula (I) have antifungal properties.

Abstract: Peptides cyclized via disulfide or lactam bridges are disclosed. The peptides exhibit melanocortin-4 receptor agonist activity and are useful for treating obesity.

Abstract: A subject of the invention, in all possible isomer forms as well as their mixtures, is the compounds of formula (I): in which either R1: H or CH3 and R2: cyclohexyl substituted by an amine, a (CH2)b-C?N radical or R1 and R2 together with the nitrogen which carries them form a ring with 3, 4 or 5 carbons optionally substituted by an amine R3: hydrogen, methyl or hydroxyl R4: hydrogen or hydroxyl R: represents a linear, branched or cyclic chain T: hydrogen, methyl, CH2CONH2, CH2C?N, a (CH2)2NH2 or (CH2)2Nalk+X? radical, X halogen and alk alkyl Y: hydrogen, hydroxyl, halogen or OSO3H, W: H or OH, Z: H, CH3. The compounds of formula (I) have antifungal properties.

Abstract: Saponins of formula (I), a stereoisomeric form thereof or a pharmaceutically acceptable addition salt thereof, wherein R1 to R12 have the meaning given in the description, can be isolated from plants of the family Myrsinaceae and used, to decrease the infectiousness of and reduce the mortality associated with protozoan parasites of the genus Leishmania which are responsible for a group of conditions known as leishmaniases.

Abstract: The invention relates to a process for the conversion of echinocandin class of peptides to their C4-homotyrosine monodeoxy analogues, particularly mulundocandin to deoxymulundocandin, which consists of a single step selective reduction of C4-htyr (homotyrosine) hydroxyl group of echinocandins to their monodeoxy analogues under neutral conditions without prior protection/deprotection of the equally facile C5-Orn (ornithine) hydroxyl group and purification of the monodeoxy compound from the crude reaction mixture.

Abstract: The present invention relates to a cyclosporin analog of the following formula (I) or a pro-drug or pharmaceutically acceptable salt thereof: In particular, residue A maybe represented by either formula A1 or A2 as illustrated below: where X and Y are defined herein. In a second embodiment, the present invention relates to pharmaceutical compositions comprising pro-drugs or pharmaceutically acceptable salts of the compounds of the present invention and the use thereof for treating autoimmune diseases or for the prevention of organ transplantation rejection in a subject. In a third embodiment, the present invention relates to processes for the production of novel cyclosporin analogs of the present invention.

Abstract: Calcitonins and calcitonin derivatives such as are employed for therapy for, for example, osteoporosis. Paget's disease or hypercalcemia. The calcitonins and calcitonin derivatives are distinguished by a bridging of the amino acids present in the positions 17 and 21. In this case, by means of a suitable choice of the amino acids present in these positions an 18- or 19-membered ring is produced. This ring leads to an increased conformational stability and to an increased activity of the modified calcitonin. A particularly suitable hCt (human Ct) analog is the cyclo17,21-[Asp17, Orn21]-hCt according to the invention having a 19-membered ring structure between the lactam-bridged Asp17 and Orn21.

Abstract: This invention relates to new polypeptide compound represented by the general formula (I) wherein R1, R2, R3, R4, R5 and R6 are as defined in the description or a salt thereof which has antimicrobial activities (especially, antifungal activities), inhibitory activity on &bgr;-1,3-glucan synthase, to process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for prophylactic and/or therapeutic treatment of infectious diseases including Pneumocystic carinii infection (e.g. Pneumocystis carinii pneumonia) in a human being or an animal.

Abstract: The present invention relates to methods for treating alopecia and stimulating hair growth and pharmaceutical compositions using nonimmunosuppressive [&ggr;-hydroxy-methylleucine4] cyclosporin A having superior hair growth-promoting effect, wherein the hydroxyl group is added to the carbon position of No. 4 methylleucine of cyclosporin A by the microorganism.

Abstract: The present invention describes an isolated macrocycle having the formula: where d is an integer from 0 to about 100; A, B, and each D are the same or different and are selected from the group consisting of each R1 is the same or different and is a bivalent alkylene moiety; each R2 is the same or different and is a bivalent alkylene moiety; and each R3 is the same or different and is selected from the group consisting of a hydrogen atom and an alkyl moiety. Methods for producing these macrocycles are also described. The macrocycles of the present invention can be used as arthropod repellents.

Abstract: The present invention provides a cyclic lipopeptide acrylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.

Abstract: The invention concerns antimicrobial cyclic peptides and peptide analogs having relatively low hemolytic activity. Peptides of the invention are effective in killing and/or inhibiting growth of a number of microorganisms, including gram-positive bacteria, gram-negative bacteria, fungi and mycoplasma. Also disclosed are methods for inhibiting or killing such microorganisms, and therapeutic preparations for such inhibiting or killing.

Abstract: Superpotent calcitonin analogs have greatly increased hypocalcemic action in vivo. These calcitonins and calcitonin derivatives are employed for the therapy of, for example, osteoporosis, Paget's disease or hypercalcemia. The calcitonins and calcitonin derivatives are distinguished by a bridging of the amino acids present in the positions 17 and 21. By means of suitable choice of the amino acids present in these positions an 18-membered or 19-membered ring is produced. This ring leads to an increased conformational stability and to an increased activity of the modified calcitonin. A particularly suitable hCt (human calcitonin analog) is a cyclo17,21-[Asp17, Orn21]-hCt having a 19-membered ring structure between the lactam-bridged Asp17 and Orn21.

Abstract: Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N&agr;(&ohgr;-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N&agr;(&ohgr;-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is specifically exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.

Abstract: The invention relates to lipopeptides with very homologous amino-acid sequences but different fatty acid residues (lipid portion) which are synthesized by Actinoplanes sp. during fermentation and are released into the culture medium, to a process for isolating the lipopeptides from the culture medium and purifying them, to the use of the lipopeptides as pharmacologically active substances, in particular against Gram-positive bacteria, and to Actinoplanes sp. DSM 7358 for producing the abovementioned lipopeptides.

Abstract: The present invention provides a cyclic lipopeptide acylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.

Abstract: Peptides useful in the regulation of calcium metabolism are disclosed. Also disclosed are pharmaceutical compositions of matter containing such peptides as well as a method for the regulation of calcium metabolism in a patient in need of such treatment. The peptides contain modified or unmodified portions of an amino acid sequence at the 8- to 32-positions of native calcination.

Abstract: The invention relates to compositions which are useful for inhibiting ribonucleotide reductase enzymes, including the mammalian ribonucleotide reductase enzyme. The compositions include, but are not limited to, linear peptides, cyclic peptides, peptide analogs, and peptidomimetics. Methods of using the compositions of the invention to treat cancer and viral and bacterial infections are disclosed.

Abstract: Certain bisamine compounds which have a cyclohexapeptidyl nucleus and which are found to have antibiotic activity with physical properties suitable for direct use in therapeutic compositions are described. A novel process for their preparation is also described.

Abstract: This invention relates to radiolabeled reagents, including specific-binding peptide embodiments thereof, and methods for producing and using such reagents. Specifically, the invention relates to reagents for preparing scintigraphic imaging agents for imaging sites in a mammalian body. Reagents, methods and kits for making such reagents, and methods for using such reagents labeled with technetium-99m (Tc-99m) via Tc-99m binding moieties comprising said reagents, are provided. In particular, the specific-binding peptides and Tc-99m binding moieties comprising the reagents of the invention are covalently linked to a polyvalent linker moiety, so that the polyvalent linker moiety is covalently linked to a multiplicity of the specific-binding peptides, and the Tc-99m binding moieties are covalently linked to a plurality of the specific-binding peptides, the polyvalent linker moiety, or to both the specific-binding peptides and the polyvalent linker moiety.

Abstract: Certain propanolamine compounds are described which have a cyclohexapeptidyl nucleus and which possess antibiotic activity with physical properties suitable for direct use in therapeutic compositions. A process for their preparation is also described.

Abstract: Certain propanolamine compounds which have a cyclohexapeptidyl nucleus and which are found to have extremely active antibiotic activity with physical properties suitable for direct use in therapeutic compositions are described. A novel process for their preparation is also described.

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. The invention also relates to the use of known compounds which are histone deacetylase inhibitors as antiprotozoal agents.

Abstract: A compound having the formula ##STR1## in which R.sub.1 is an aminoalkyl group and ##STR2## is an acyl group and salts thereof having high antibiotic activity and being substantially free of lytic activity are described.

Abstract: Novel amino acid conjugates of cyclohexa-peptidyl amines having the formula ##STR1## and having antifungal and antiparasital properties are described. The compounds exhibit less acute toxicity than the free amines.

Abstract: Straight or cyclic pentapeptides with receptor affinity to .mu. or .delta. opioid receptors having a primary sequence backbone of Tyr-X-Phe-Leu-Z, Seq. ID Nos. 1, 2, and 3. X and Z can be covalently coupled to provide a heterocyclic structure according to the following conditions:i) when the pentapeptide is straight X is selected from the group consisting of Ser, Gly, Pro, AMCA and D-Ala and Z is selected from the group consisting of Glu, Gln or amino derivatives of Glu or Gln, Seq. ID No. 1, with the proviso that if X is Ser, then Z is Glu or amino derivatives of Glu; andii) where the pentapeptide is cyclic X is selected from the group consisting of D- or L-2,4-diaminobutyric acid, D- or L-lysine, D- or L-ornithine and D or L-cysteine and Z is selected from the group consisting of Gln or Glu or amino derivatives of Gln or Glu, Seq. ID No. 2, and 3, with the proviso that if X is D-or L-Cys, then Z is Cys, Seq. ID No. 3.

Abstract: A method of patterning a layer of reflective material, such as a layer of conductor metal, using a layer of antireflection coating material sandwiched between two layers of photoresist. A first layer of photoresist is formed on an integrated circuit wafer and provides a planar surface for subsequent layers of material. A layer of antireflection coating material is formed on the layer of first photoresist and a layer of second photoresist is formed on the layer of antireflection coating material. The layer of second photoresist is selectively exposed and developed. The layer of antireflection coating material is patterned using dry etching and the patterned layer of second photoresist as a mask. The layer of first photoresist is then patterned using dry etching and the patterned layer of antireflection coating material as a mask. The layer of reflecting material is then patterned using dry etching and the patterned layer of first photoresist as a mask. The patterned layer of first photoresist is then removed.

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 describes cyclic peptide compounds which modulate integrin mediated adhesion. These compounds can inhibit both .beta..sub.1 and .beta..sub.2 mediated adhesion. The invention further relates to therapeutic uses for these compounds in the treatment of adhesion related pathologies.

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: There are disclosed compounds of the general formula ##STR1## wherein all substituents are defined herein. The compounds are useful as antibiotic and antifungal agents.

Abstract: Analogs of porcine Vasoactive Intestinal Peptide are disclosed. The analogs have been cyclized by the covalent attachment, via an amide bond, of the side-chain carboxy terminus of one amino acid in the peptide chain to the side-chain amino terminus of another amino acid in the peptide chain. The claimed compounds are useful for the treatment of asthma.

Abstract: Provided are pharmaceutical formulations, and methods of inhibiting fungal and parasitic activity using a compound of formula I: ##STR1## wherein: R.sup.z1 is hydrogen, --CH.sub.2 OH, --CHOHCH.sub.3 or --CHOHCH.sub.2 C(O)NH.sub.2 ;R.sup.z2 is hydrogen, --CH.sub.2 OH or --CHOHCH.sub.3 ;R.sup.z3 is hydrogen or methyl;R.sup.x1 is hydrogen, hydroxy or O--R.sup.x1' ;R.sup.x1' is C.sub.1 -C.sub.6 alkyl, benzyl, --(CH.sub.2).sub.2 Si(CH.sub.3).sub.3, --CH.sub.2 CH.dbd.CH.sub.2, --CH.sub.2 CHOHCH.sub.2 OH, --(CH.sub.2).sub.a COOH, --(CH.sub.2).sub.b NR.sup.w1 R.sup.w2, --(CH.sub.2).sub.c POR.sup.w3 R.sup.w4 or --[(CH.sub.2).sub.2 O].sub.d --(C.sub.1 -C.sub.6)alkyl;a, b and c are independently 1, 2, 3, 4, 5 or 6;R.sup.w1 and R.sup.w2 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or R.sup.w1 and R.sup.w2 combine to form --CH.sub.2 (CH.sub.2).sub.e CH.sub.2 --;R.sup.w3 and R.sup.w4 are independently hydroxy, or C.sub.1 -C.sub.6 alkoxy;d is 1 or 2;e is 1, 2 or 3;R.sup.x2, R.sup.y1, R.sup.y2, R.sup.y3 and R.sup.

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: 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.

Abstract: Certain propionitrile compounds which have a cyclohexapeptidyl nucleus and which are found to have antibiotic activity with physical properties suitable for use in therapeutic compositions are described. A novel process for their preparation is also described.

Abstract: Disclosed herein are analogues of the luteinizing hormone-releasing hormone (LH-RH), which are potent antagonists of LH-RH. These peptides inhibit the release of gonadotropins from the pituitary in mammals, including humans and possess antitumor activity.Formula I represents peptides which are within the scope of this invention:X--R.sup.1 --R.sup.2 --R.sup.3 --Ser--R.sup.5 --R.sup.6 (AY.sub.2)--Leu--Arg--Pro--D--Ala--NH.sub.2 Iand the pharmaceutically acceptable salts thereof, whereinR.sup.1 is D-Phe, D-Phe(4Cl), D-Nal(1) or D-Nal(2),R.sup.2 is D-Phe or D-Phe(4HI),R.sup.3 is D-Trp, D-Phe, D-Phe(4HI), D-Nal(1), D-Nal(2) or D-Pal(3),R.sup.5 is Tyr or Arg,R.sup.6 is D-Lys or D-Orn,HI is fluoro, chloro or bromoX is a lower alkanoyl group of 2-5 carbon atoms,A is a diaminoacyl residue having the formula ##STR1## where m is 0 or 1,n is 0 or 1,Y is Y.sup.1 or Y.sup.2, whereinY.sup.

Abstract: A method for the treatment of Pneumocystis carinii, the causative agent of pneumonia of particular severity to immune compromised patients such as those with acquired immune deficiency syndrome (AIDS), by administering a lipophilic cyclohexapeptide compound of the general formula ##STR1## wherein the R groups are fully defined in the text, is described. Compositions suitable for the treatment of P. carinii are also disclosed.

Abstract: Various cyproheptadine derivatives sensitize multidrug resistant cells to certain chemotherapeutic agents. As such, these cyproheptadine derivatives are useful as adjuncts in the reversal of multidrug resistance in mammalian tumor cells either as compounds, pharmaceutically acceptable salts, or pharmaceutical composition ingredients in combination with anticancer chemotherapeutic agents or compounds.

Abstract: Linear and cyclic Growth Hormone Releasing Factor Analogs and a method for stimulating the release of Growth Hormone in subjects by administering to the subject an effective amount of the compounds of the invention.

Abstract: A bleomycin conjugate for use in targeting a compound to a body tumor. The conjugate includes an oxidized bleomycin/cobalt(III) complex and the compound to be targeted joined to the complex through a monodentate cobalt/sulfur coordinate bond. Also disclosed are methods for preparing the conjugate, and for targeting the compound to a body tumor, for purposes of tumor radioimaging or therapy.