Abstract: The present invention describes methods for inhibiting angiogenesis in tissues using vitronectin ?v?5 antagonists. The ?v?5-mediated angiogenesis is correlated with exposure to cytokines including vascular endothelial growth factor, transforming growth factor-? and epidermal growth factor. Inhibition of ?v?5-mediated angiogenesis is particularly preferred in vascular endothelial ocular neovascular diseases, in tumor growth and in inflammatory conditions, using therapeutic compositions containing ?v?5 antagonists.

Abstract: Monomeric monocyclic peptide inhibitors and dimeric bicyclic peptide inhibitors based on exposed loop fragments of a growth factor protein, such as loop 1, 2 or 3 of VEGF-D, and methods of making them are described as well as pharmaceutical compositions containing them and methods utilizing them.

Abstract: The present invention relates to novel semi-synthetic cyclosporin analogs for the prevention of organ transplantation rejection and the treatment of immune disorders and inflammation, their use as pharmaceuticals and pharmaceutical composition comprising them, as well as the processes for the their production. The present invention provides a cyclosporin compound of the following Formula (1) or its pharmaceutically acceptable salt, ester or prodrug thereof. In the compound of Formula (1), moiety “A” is Wherein “X” and “Y” are defined herein.

Abstract: The present invention relates to methods of treating or preventing an inflammatory or immune disorder in a subject while eliminating or reducing the toxicity associated with the administration of cyclosporin A, comprising systemically administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula (I) or a pharmaceutically acceptable salt, ester or prodrug thereof, in combination with a pharmaceutically acceptable carrier or excipient: in Formula (I), the formula for residue A is:

Abstract: The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISATX247, and derivatives thereof. Mixtures of ISATX247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISATX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. The ratio of isomers in a mixture may range from about 10 to 90 percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the (Z)-isomer, based on the total weight of the mixture.

Abstract: A pro-drug comprising a cyclic undecapeptide wherein the peptide chain thereof comprises at least one amino acid residue, useful as a medicinal product, including use for treatment of pathological conditions of the eye.

Abstract: The present invention discloses a hair growth promoting agent comprising a cyclosporin derivative as an active ingredient, and more particularly, a hair growth promoting agent comprising a cyclosporin A derivative in which sarcosine is substituted with thiosarcosine in the 3-position as an active ingredient.

Abstract: The present invention relates to a cyclosporin analog of the following formula (I) or its pro-drug or pharmaceutically acceptable salt: In formula I, the formula for residue A is: where X and Y are defined according to the claimed invention the present invention also relates to pharmaceutical compositions comprising pro-drugs or pharmaceutically acceptable salts of the compounds of the present invention and the use thereof for treating an inflammatory or immune disorder in a subject need of such treatment.

Abstract: The invention relates to new basic amino acid derivatives of general formula I and the preparation and use thereof in treatment of pain. The compounds have histogranin-like antinociceptive, morphine potentiating and COX-2 induction modulating activities.

Abstract: A novel class of analogs which exhibit both high affinity and selectivity for Neuromedin B and Somatostann receptors are claimed. One example is Nal-Tyr-cyclo(D-Cys-D-Trp-Lys-D-Cys)-Abu-Nal-NH2.

Abstract: The present invention discloses a family of cyclic peptide monomers and supramolecular cyclic peptide structures comprising chromophore residues which possess electronic and electro-optic properties for producing molecular scale electronic and photonic devices made from such materials. More particularly, this invention provides for cyclic peptide nanotube structures formed from a plurality of stacked cyclic peptides comprising chromophore residues that provide molecular scale electronic conductivity and non linear optical behavior. The stackable cyclic peptide is represented by the general formula where R1 is H, CH3 or alkyl; where at least one R2 is a chromophore; where R3 is H, CH3 or a polar or non-polar organic functional group used for controlling peptide stacking and solubility; where n equals 1 or 2; where m equals 4 or 6; and where a first adjacent amino acid residue has an ?-carbon chirality of L and a second adjacent amino acid residue has an ?-carbon chirality of D.

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 ?-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 invention relates to linear and cyclic peptide and pseudopeptide compounds useful as analgesics, pharmaceutical compositions comprising such compounds, the use of the compounds and the compositions in the treatment of pain, and commercial packages containing such compounds and compositions.

Abstract: The present invention relates to novel Aerothricins represented by the Formula (I), and pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition comprising an Aerothricin of the Formula (I) and a pharmaceutically acceptable carrier. Furthermore, the present invention relates to the use of such Aerothricins for the preparation of medicaments, as well as to processes for the preparation of the Aerothricins of the Formula (I).

Abstract: The present invention relates to a cyclosporin analog of the following formula (I) or a pro-drug or pharmaceutically acceptable salt thereof: 1

Abstract: Compositions and methods are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction. In one embodiment, a peptide-based composition including the peptide sequence Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH is administered. Methods of administration include injection, oral, nasal and mucosal administration.

Abstract: The invention provides methods and compositions relating to DNA Fragmentation Factor (DFF) polypeptides and related nucleic acids. More particularly, the present invention provides the sequence for the active subunit of DFF. The polypeptides may be produced recombinantly from host cells transformed from the disclosed DFF encoding nucleic acids or purified from human cells. The invention provides isolated DFF, hybridization probes and primers capable of specifically hybridization with the disclosed DFF genes, DFF-specific binding agents such as specific antibodies, and methods of making and using the subject compositions.

Abstract: The present invention discloses a hair growth promoting agent comprising a cyclosporin derivative as an active ingredient, and more particularly, a hair growth promoting agent comprising a cyclosporin A derivative substituted in the 3-position as an active ingredient.

Abstract: Disclosed is a hair growth promoting agent including a cyclosporin derivative as an active ingredient, and more particularly, a hair growth promoting agent including a cyclosporin A derivative substituted in the 3-position as an active ingredient.

Abstract: Object of the invention is a process for the chromatographic purification of cyclosporin A from a crude product containing cyclosporin complex by using a column filled with silica gel and by the application of multistep chromatography with a column filled with normal phase silica gel and by a solvent mixture containing toluene as the major component.

Abstract: A ligand for a neuropeptide Y receptor which has the formula: Ac-Ala-Arg-Ala-Ala-Leu-Asn-Ala-Ala-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:1), or Ac-Ala-Arg-His-Tyr-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:2), or Ac-Leu-Ala-His-Tyr-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:3), or Ac-Leu-Arg-Ala-Tyr-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:4), or Ac-Leu-Arg-His-Ala-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:5), or Ac-Leu-Arg-His-Tyr-Ala-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2(SEQ ID NO:6), or Ac-Leu-Arg-His-Tyr-Leu-Ala-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:7), or Ac-Leu-Arg-His-Tyr-Leu-Asn-Ala-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:8), or Ac-Leu-Arg-His-Tyr-Leu-Asn-Leu-Ala-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:9), or Ac-Ala-Arg-His-Ala-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:10), or Ac-Leu-Arg-Ala-Ala-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:11), wherein Ac is acetyl.

Abstract: By virtue of the present invention, there is provided methods and compositions for interfering with the proliferation of cells infected and/or transformed by papillomaviruses. The processes and compositions of this invention may be used to treat any mammal, including humans. According to this invention, mammals are treated by the pharmaceutically acceptable administration of an E2 peptidomimetic to reduce the symptoms of the specific papillomavirus-associated disease, or to prevent their recurrence.

Abstract: Methods of inhibiting osteoclastogenesis and the activity of osteoclasts are disclosed. Methods of treating patients who have diseases characterized bone loss are disclosed. According to the methods, an amount of a TRANCE/RANK inhibitor effective to inhibit osteoclastogenesis is administered to the patient. Pharmaceutical compositions which comprise TRANCE/RANK inhibitor in an amount effective to inhibit osteoclastogenesis. Methods of modulating dendritic cell maturation, T cell proliferation, and/or CD40 receptor systems in an individual are disclosed. The methods comprise the step of administering to the individual an amount of a TRANCE/RANK inhibitor effective to modulating dendritic cell maturation, T cell proliferation, and/or CD40 receptor systems.

Abstract: A cyclic tetrapeptide compound and use thereof.

Abstract: Cyclic peptides inhibit LFA-1 interaction with ICAM-1 and are useful in treatment of hematopoietic neoplasms and in adjunct therapy in prevention of retinoic acid syndrome and diseases involving emigration of leukocytes into organ tissue.

Abstract: Cyclic homodetic peptides having a repeating D-L-chirality motif are shown to have a stable disk conformation with the amino acid side chains extending radially outward and the carbonyl and amino groups extending axially upward or downward. Such cyclic peptides can be employed as subunits in the assembly of molecular tubes. Cyclic peptides having a repeating D-L-chirality motif and lacking mutually repulsive side-chains are shown to stack atop one another in an anti-parallel fashion and are shown to be held together by the formation of &bgr;-sheet hydrogen bonding. The stacked cyclic peptides form a molecular tube having a central channel. The diameter of the channel is determined by the size cyclic peptide. If the cyclic peptide includes ionizable amino acid residues, e.g. glutamic acid or lysine, assembly and disassembly of the molecular tubes can be controlled by varying the pH. If the cyclic peptide includes hydrophobic amino acid residues, the molecular tube will insert into a lipid membrane.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R21, R22, R3, R4, D and A are as defined herein, or a pharmaceutically acceptable salts or ester thereof.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

Abstract: Compositions and methods are provided for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction. In one embodiment, a peptide-based composition including the peptide sequence Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH is administered. Methods of administration include injection, oral, nasal and mucosal administration.

Abstract: The invention relates to linear and cyclic peptide and pseudopeptide compounds useful as analgesics, pharmaceutical compositions comprising such compounds, the use of the compounds and the compositions in the treatment of pain, and commercial packages containing such compounds and compositions.

Abstract: Disclosed in a peptide represented by the following formula (I):

Abstract: By virtue of the present invention, there is provided methods and compositions for interfering with the proliferation of cells infected and/or transformed by papillomaviruses. The processes and compositions of this invention may be used to treat any mammal, including humans. According to this invention, mammals are treated by the pharmaceutically acceptable administration of an E2 peptidomimetic to reduce the symptoms of the specific papillomavirus-associated disease, or to prevent their recurrence.

Abstract: Helical oligomer and polymer compositions that form nanotubes are described. The compositions comprise a plurality of aromatic substituents linked by at least one amide group. The compositions have a curved backbone due to intramolecular hydrogen bonds that rigidify the amide linkage of each amide group to each aromatic substituent and due to an interaction between the aromatic substituents such that the curved backbone is stabilized. The helical compositions are formed by ridigifying the amide group, which is flanked on each side by the aromatic substituents, by introducing intramolecular hydrogen bonds into a linkage between the amide group and each aromatic substituent such that the compositions fold into a helical shape when the amide linkages are meta to each other.

Abstract: An immunoregulatory molecule that regulates costimulatory signal transduction through interaction with the molecules involved in costimulatory signal transduction present on antigen presenting cells and/or T cells in the activation of T cells by antigen presenting cells and a process for preparing the same are provided. Said immunoregulatory molecule comprises a peptide which has two cysteine (Cys) residues forming Cys-Cys linkage and comprises at least six amino acid residues between said Cys-Cys linkage. Said immunoregulatory molecule is obtained by screening a phage random peptide library with a monoclonal antibody to CTLA-4 on T cells involved in costimulatory signal transduction.

Abstract: Object of the invention is a process for the chromatographic purification of cyclosporin A from a crude product containing cyclosporin complex by using a column filled with silica gel and by the application of multistep chromatography with a column filled with normal phase silica gel and by a solvent mixture containing toluene as the major component.

Abstract: A cyclic tetrapeptide derivative represented by the general formula (I): wherein: R11, R12, R21 and R22 independently denote a monovalent group selected from hydrogen, a linear or branched alkyl group with 6 or less carbon atoms, benzyl group, 4-methoxybenzyl group, 3-indolylmethyl group, (N-methoxy-3-indolyl) methyl group, (N-formyl-3-indolyl)methyl group, etc.; R3 denotes a divalent group selected from a linear chained hydrocarbon group with 3 or 4 carbon atoms, or the linear branched hydrocarbon group having a branched chain added to the chain, or a divalent group substituted with a heteroatom; R4 denotes a divalent chained hydrocarbon group with 4 to 6 carbon atoms, or a divalent group derived from said hydrocarbon group by addition etc.

Abstract: By virtue of the present invention, there is provided methods and compositions for interfering with the proliferation of cells infected and/or transformed by papillomaviruses. The processes and compositions of this invention may be used to treat any mammal, including humans. According to this invention, mammals are treated by the pharmaceutically acceptable administration of an E2 peptidomimetic to reduce the symptoms of the specific papillomavirus-associated disease, or to prevent their recurrence.

Abstract: The present invention relates to peptidomimetics capable of inhibiting CD28 and/or CTLA-4 interaction with CD80 (B7-1) and CD86 (B7-2) and having a core amino acid sequence, LeuMetTyrProProProTyrTyr, corresponding to residues 2 to 9 of SEQ ID NO:1. The present invention also relates to pharmaceutical compositions and a method of treating pathologies and disorders which are improved by inhibition of CD28 and/or CTLA-4 interaction with CD80 and CD86.

Abstract: The present invention relates to a novel chromatographic process which is suitable for the purification of cyclosporin-containing crude extracts on industrial scale. In this process, the conventional preparative chromatographic separation methods are completely or at least partially replaced by the simulated moving bed method (SMB). The cyclosporin A obtained corresponds both to the quality requirements of USP XXIII and of EUROPEAN PHARMACOPOEIA, 2nd Edition 1995.

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

Abstract: The present invention relates to peptides and peptide analogues designed from a binding loop of a member of the tumor necrosis factor receptor (TNF-R) superfamily. In particular, it relates to cyclic peptides and peptide analogues designed from a binding loop of TNF-R which inhibit TNF binding to its cellular receptors, and methods of making and using such compounds to inhibit the biological activities of TNF.

Abstract: This invention provides a physiologically active substance having a strong dipeptidyl peptidase IV inhibitory activity. The physiologically active substance sulphostin is obtained by culturing a microorganism belonging to the genus Streptomyces and having an ability to produce the physiologically active substance sulphostin, producing and accumulating this substance in the cultures, and harvesting it from the cultures.

Abstract: Cyclic penta- and hexa-peptide libraries containing one or more known amino acids, one or more randomized amino acids and a conformationally constraining element are disclosed. These peptide libraries may be used for screening for new bioactive peptides and for elucidating structural information pertinent to drug design.

Abstract: A new method of measuring blood levels of immunophilin-binding pharmaceuticals, e.g., cyclosporins, rapamycins, and FK506 compounds is provided, comprising the novel step of displacing the pharmaceutical from its immunophilin by using a binding competitor, thereby eliminating the need for an extraction step and enhancing the simplicity and accuracy of the assay. Assay kits comprising a binding competitor and a receptor, e.g., a monoclonal antibody, which binds to the pharmaceutical but not significantly to the binding competitor are also provided, as are new uses of immunophilin-binding compounds as binding competitors in such assays.

Abstract: Compounds are provided that prevent the interaction of an IGF with any one of its binding proteins and not to a human IGF receptor.

Abstract: Compounds of formula A are disclosed: ##STR1## wherein R.sup.1 is aralkyl or cycloalkyl; R.sup.2 is cycloalkylmethyl, alkyl, or aralkyl;R.sup.3 is hydrogen, alkyl, substituted phenyl (including p-phenoxy-phenyl), or fluorene;R.sup.4 is hydrogen, alkyl, substituted phenyls (including 1-alkyl-4-carboxy-substituted phenyls), alkyl carboxylic acids;R.sup.5 is hydrogen or R.sup.1 and R.sup.5 taken together forming a tetrahydroisoquinoline ring or a piperidine ring.These compounds exhibit inhibitory action against fructose-1,6-bisphosphatase (FBPase) and are indicated in the treatment or management of Type II diabetes.

Abstract: The invention relates to compounds of the formula Icyclo(A-B-C-E-F-(D)-Ala) (I)in which A, 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 compounds of formula (I) cyclo[X.sub.1.sup.1 --Z.sub.1.sup.2 --X.sub.2.sup.3 --X.sub.3.sup.4 --Z.sub.2.sup.5 --X.sub.4.sup.6 ]cyclo(2.beta.-5.beta.) wherein: X.sub.1 =(D or L)Cys(Y) or (D or L)SeCys(Y), Z.sub.1 =Asp and Z.sub.2 =Dap or Z.sub.1 =Dap and Z.sub.2 =Asp and X.sub.2, X.sub.3 and X.sub.4 =natural or synthetic hydrophobic amino acids, having Z.sub.1, Z.sub.2, X.sub.2, X.sub.3 and X.sub.4 the same D or L configuration; Y=is a glycosidic group selected from the aldo and keto hexoses in the furanose or pyranose form bound to the cysteine with an .alpha. or .beta. thioacetalic bond or a cyclithol or a polyvinyl alcohol or PEG, constituted of 5 to 10 monomeric unities, bound to the cysteine with a thioether bond, are endowed of high solubility and of potent tachykinin-antagonistic activity.