Abstract: Methods are provided for treatment of cancer cells, in a regimen comprising contacting the cancer cells with an inhibitor on NGly1, optionally in combination with a direct proteasome inhibitor.

Abstract: Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.

Abstract: Peptide analogues of PYY, compositions comprising said analogues and methods of using said analogues for the treatment and prevention of metabolic disorders, for example disorders of energy metabolism such as diabetes and obesity, and for a reduction in appetite, reduction in food intake or reduction of calorie intake in a subject.

Abstract: Compounds having the Formula I and pharmaceutically acceptable salts thereof are provided in which the variables are described herein. Methods of making the compounds of Formula I are also disclosed.

Abstract: Peptides may be produced by using (A) a first amino acid or peptide, which is converted into its ionic liquid form through the formation of an ionic bond, as a substance serving as both a reaction solvent and a reaction starting material; and reacting the first amino acid or peptide with (B) an ester of second amino acid or peptide, in the absence of any peptide hydrolase or any condensation agent, in the presence of water in an amount of not more than 20% by mass relative to the total mass of the reaction system to form a peptide bond between the first amino acid or peptide and the second amino acid or peptide. By means of this process, it is possible to synthesize a peptide at a high concentration and at a high yield, and this method is excellent for producing peptides on an industrial scale.

Abstract: The present invention relates to a system for intracellular cargo delivery, named NickFect, comprising at least one component A, which is attached covalently to cell penetrating peptide B and/or peptide or non-peptide construct C. The said delivery system NickFect relates to chemically modified new cell-penetrating peptides (CPP) non-covalently or covalently complexed with cargo for efficient cellular.

Abstract: The present invention relates to bradykinin receptor modulators and pharmaceutical compositions thereof for use as a medicament for modulating collateral blood vessel growth of collateral arteries and/or other blood vessels of pre-existing arterial networks. The bradykinin receptor modulators of arteriogenesis are applicable in the treatment and/or prevention of disorders associated with defective blood flow or blood vessel malformation. A preferred aspect of the invention relates to bradykinin receptor agonists for use as a medicament for the prevention of cardiovascular ischemic disease in a patient at risk thereof. Further, the invention relates to a bradykinin receptor agonist for use in a method for treating a cardiovascular ischemic disease in a patient in need thereof, wherein said cardiovascular ischemic disease is a peripheral limb disease.

Abstract: The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a univalent vehicle, including peptides conjugated to univalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.

Abstract: The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a multivalent vehicle, including peptides conjugated to multivalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.

Abstract: A GABA (gamma-aminobutyric acid) release-inhibiting agent in the cerebellum and a composition for treating pathological symptoms caused by over-release of GABA in the cerebellum, each comprising a Bestrophin 1(Best1) channel inhibitor as an active ingredient; a GABA release-promoting agent in the cerebellum and a composition for treating pathological symptoms caused by the deficit of GABA in the cerebellum, each comprising a Best1 channel activator as an active ingredient; and a method for screening a GABA release-regulating agent in the cerebellum, which uses Best1 channel as target, are provided.

Abstract: Stabilized radiopharmaceutical formulations are disclosed. Methods of making and using stabilized radiopharmaceutical formulations are also disclosed. The invention relates to stabilizers that improve the radiostability of radiotherapeutic and radiodiagnostic compounds and formulations containing them. In particular, it relates to stabilizers useful in the preparation and stabilization of targeted radiodiagnostic and radiotherapeutic compounds, and, in a preferred embodiment, to the preparation and stabilization of radiodiagnostic and radiotherapeutic compounds that are targeted to the Gastrin Releasing Peptide Receptor (GRP-Receptor).

Abstract: The disclosed methods address the identification and monitoring of cancer in a subject using serum peptide profiles. Such profiles allow the detection of the differential presence of certain serum peptide markers in comparison with controls. The profiles can be determined employing mass spectrometry.

Abstract: Methods for diagnosing a kidney disease, or the risk thereof, in a subject are provided. The methods comprise determining an amount of at least one peptide biomarker disclosed herein in a biological sample from the subject and comparing the amount of the at least one peptide in the sample with a control level, wherein if the amount determined is different than the control level, the subject is diagnosed as having, or at an increased risk of developing, the kidney disease.

Abstract: Provided is a method for the use of a bradykinin B1 receptor antagonist of formula I: X-CO-Aaa0-Aaa1-Aaa2-Aaa3-Gly-?(Me)Phe-Ser-D-?Nal-Aaa8-OH (I) or a pharmaceutically acceptable salt or hydrate thereof wherein: X is CnH2n+1 or CiH2i—C6H5, where n is an integer from 1 to 3, and i is an integer from 0 to 3; Aaa0 is Lys, Orn or Cit; Aaa1 is Arg or Cit, and preferably Arg; Aaa2 is Oic, Hyp or Pro, and preferably Oic; Aaa3 is Pro or Oic, and preferably Pro; and Aaa8 is Ile, Leu or Nle, and preferably Ile, for the treatment of metastases, cancers and/or chemotherapy-induced neuropathies, comprising the administration of the compound to a patient in need of such treatment. Also provided are compositions containing such antagonists and their thereof.

Abstract: The invention provides bradykinin antagonists and pharmaceutically acceptable salts thereof having anti-cancer activity. These anti-cancer compounds are particularly useful for inhibiting the growth of lung and prostate cancers.

Abstract: The invention provides methods for treating and/or preventing ocular disorders associated with increased intraocular pressure comprising administering a bradykinin B2 receptor agonist to a patient in need thereof.

Abstract: The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a multivalent vehicle, including peptides conjugated to multivalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.

Abstract: The invention provides bradykinin antagonists and pharmaceutically acceptable salts thereof having anti-cancer activity. These anti-cancer compounds are particularly useful for inhibiting the growth of lung and prostate cancers.

Abstract: Tachykinin peptide isolated and purified from the posterior salivary gland of the mollusk Octopus vulgaris. The tachykinin peptide provides a new approach for developing medicaments and pesticides through studies on the structural activity correlation at the molecular level, is characterized by: (1) number of amino acid residues is 12; (2) N terminal of the peptide is Lys; (3) an amino acid sequence of 5 amino acids from C-terminal is represented by the following amino acid sequence: Phe-Xaa-Gly-Leu-Met (SEQ ID NO: 6), (wherein, Xaa is Val, lie, Phe or Tyr), especially following amino acid sequences are provided: Lys-Pro-Pro-Ser-Ser-Ser-Glu-Phe-Val-Gly-Leu-Met (SEQ ID NO: 1), Lys-Pro-Pro-Ser-Ser-Ser-Glu-Phe-Ile-Gly-Leu-Met (SEQ ID NO: 2).

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: The present invention relates to amino acid sequences for novel tachykinin polypeptides and base sequences encoding them, agonists and antagonists of such polypeptides, pharmaceutical compositions comprising them, and the like.

Abstract: The invention relates to compounds and methods for inhibiting human platelet aggregation, thrombosis and cell activation mediated by PAR1 and PAR4 using peptide analogs of Arg-Pro-Pro-Gly-Phe that contain one or more amino acid substitutions. The invention also includes screening methods for identifying compounds that inhibit thrombin mediated activities.

Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X[Formula I] wherein X is a linker group having 2–5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.

Abstract: The present invention relates to novel antagonists to a B1-bradykinin (B1-BK) receptor which have a good affinity and selectivity therefor, some of which being at least partially resistant to enzymatic degradation. The synthesis of the B1 receptors is induced during inflammation. Symptoms associated with inflammation (elevated hydrostatic pressure and plasma leakage or extravasation) have been observed in diabetic animal models (streptozotocin-induced diabetes (STZ)) as well as in spontaneously hypertensive rats (SHR). The present inventors confirm the presence of B1-BK receptors in these two models. B1-BK antagonists abolished the vasocontraction induced by B1-BK in SHR and STZ, and reduced the glycemia of diabetic animals to normal levels.

Abstract: An object of the present invention is to provide a protein useful as a sphingomyelin detecting probe, which specifically recognizes sphingomyelin and has low cytotoxicity. The present invention provides a protein which has an amino acid sequence having, as the amino acid sequence from the 1st to the 48th amino acid, the amino acid sequence from the 1st to the 48th amino acid in Lysenin 1, and as the amino acid sequence from the 49th to the 298th amino acid, the amino acid sequence from the 51st to the 300th amino acid in Lysenin 3; and a protein which is obtained by deleting N terminal and/or C terminal from earthworm toxins Lysenin 1 or 3, and which specifically recognizes sphingomyelin.

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with a D-configuration hydroxyproline ether or thioether converts bradykinin agonists into bradykinin antagonists. The invention further includes the intermediate compounds and additional modifications at other positions within the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X  [Formula I] wherein X is a linker group having 2-5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.

Abstract: The substitution of the L-Pro at the 7-position with D-Phe or D-Tic and substitution of the L-Phe at the 8-position with hydroxyproline ethers and thioethers of the peptide hormone bradykinin and other additional substituted analogs of bradykinin converts bradykinin agonists into bradykinin antagonists. The invention further includes additional modifications at other positions within the novel 7- and 8-position modified bradykinin antagonists, which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract: The invention relates to the use of bradykinin antagonists for the production of pharmaceuticals for the treatment and prevention of Alzheimer's disease. Suitable bradykinin antagonists are peptides which inhibit the effects of the Alzheimer's protein amyloid (&bgr;/A4) on isolated endothelial cells. A particularly suitable peptide is H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH (HOE 140) and its physiologically tolerable salts.

Abstract: A regenerated collagen fiber is subjected to water-insolubilizing treatment with a monofunctional epoxy compound to produce a water-insolubilized regenerated collagen fiber which can substantially maintain the color and the high knot tenacity, inherent in the collagen. Where the monofunctional epoxy compound is an epihalohydrin, a regenerated collagen fiber can be treated with this epihalohydrin and a sulfur compound to produce a water-insolubilized regenerated collagen fiber which can be permanent-wave set. In addition, the water-insolubilized regenerated collagen fiber can be converted into a fiber which can be permanent-wave set, by introducing a disulfide linkage into carboxylic groups of the collagen, which remain unmodified by the insolubilizing treatment.

Abstract: A bradykinin antagonist of the formula:(BKAn)(X)(Y)where BKAn is a bradykinin antagonist peptide; Y is a pharmacore; and X is a bridging link chemically joining the BKAn and Y components.

Abstract: The present invention provides bradykin antagonists containing pentafluorophenylalanine which are therapeutically useful. Moreover, the present invention provides methods to antagonize bradykinin receptors in a mammal in need of such antagonism, comprising administering a bradykinin antagonist containing pentafluorophenylalanine. Also provided are methods to treat inflammation in a mammal in need of such inhibition, comprising administering a bradykinin antagonist containing pentafluorophenylalanine. Lastly, a method to treat cancer in a mammal in need of such inhibition, comprising administering a bradykinin antagonist containing pentafluorophenylalanine.

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.sup..alpha. (.omega.-functionalized)amino acids constructed to include a spacer and a terminal functional group. One or more of these N.sup..alpha. (.omega.-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 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: A bradykinin antagonist of the formula:(BKAn) (X) (Y)where BKAn is a bradykinin antagonist peptide; Y is a Pharmacophore; and X is a bridging link chemically joining the BKAn and Y components.

Abstract: This invention relates to a method of treating a chronic fibrogenetic liver disorder and/or an acute liver disorder and/or complications associated therewith, comprising administering to a patient a therapeutically effective amount of a bradykinin antagonist. Particular complications associated with said liver disorders include portal hypertension, decompensation phenomena such as ascites, edema formation, hepatorenal syndrome, hypertensive gastropathy and colopathy, splenomegaly and hemorrhagic complications in the gastrointestinal tract due to portal hypertension, collateral circulation and hyperemia and a cardiopathy as a result of a chronically hyperdynamic circulatory situation and its consequences.

Abstract: The present invention provides bradykinin antagonists effective to inhibit cancer cell growth. Also provided are methods of inhibiting lung cancer cell growth by administering a therapeutically effective amount of a dimerized bradykinin antagonist.

Abstract: This invention is in the field of the chemistry of targeting anticancer anthracycline derivatives. More particularly, it concerns doxorubicin (DOX) or its daunosamine modified derivatives (DM-DOX) linked covalently to analogs of peptide hormones such as LH-RH, bombesin and somatostatin. These covalent conjugates are targeted to various tumors bearing receptors for the peptide hormone analogs. The compounds of this invention are represented by General Formula Q.sup.14 --O--R--P wherein Q has the general formula ##STR1## wherein: Q.sup.14 signifies a Q moiety with a side chain at the 14 position, R-- is H or --C(O)--(CH.sub.2).sub.n --C(O)-- and n=0-7, R' is NH.sub.2 or an aromatic, saturated or partially saturated 5 or 6 membered heterocyclic compounds having at least one ring nitrogen and optionally having a butadiene moiety bonded to adjacent carbon atoms of said ring to form a bicyclic system; P is H or a peptide moiety, suitably an LHRH, somatostatin or bombesin analogs. Nevertheless where R' is NH.sub.

Abstract: The present invention relates to pharmaceutically effective heterodimers comprising a bradykinin antagonist component covalently linked to a mu-opioid agonist component.

Abstract: The present invention provides des-Arg.sup.9 bradykinin analogs which are selective B1 receptor antagonists.

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.sup..alpha. (.omega.-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N.sup..alpha. (.omega.-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 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: Bradykinin antagonists and their physiologically tolerated salts are suitable for the treatment or prophylaxis of virus diseases.

Abstract: Novel cyclic CRF antagonist peptides are created by shortening the N-terminus of a CRF family peptide by 8-11 residues and adding an acyl group. CML is preferably present in what would be the 27-position of the native CRF sequence, and D-Tyr may be incorporated at the N-terminus to facilitate labelling. The cyclizing bond is preferably created between the side chains of the residues in positions 30 and 33; but it may alternatively be created between the residues in either of positions 28 and 29 with those in positions 31 and 32 or with those in positions 32 and 33, respectively. The side chain of Lys in position 33 is preferably linked to the side chain of Glu in position 30 by a lactam bridge to form the cyclic peptide. Disclosed CRF antagonists include:(cyclo 30-33) ?Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27,40, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41),(cyclo 30-33) ?Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27,37, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41),(cyclo 30-33) ?Ac-Asp.sup.9, D-Phe.sup.

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

Abstract: Bradykinin antagonists, particularly Cys.sup.6 analogs, which have an extended hydrophobic side chain.

Abstract: The present invention provides bradykinin type peptides containing N-substituted glycines, particularly bradykinin antagonist peptides useful for the treatment of conditions mediated by bradykinin including pain and inflammation.

Abstract: Peptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the interstitial fluid compartment of the brain. Alternatively, the permeabilizer A-7 or conformational analogues can be administered sequentially with the molecule(s) of interest and these molecules can also be administered by routes other than intravascular. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive in the interstitial fluid.

Abstract: The invention relates to the use of bradykinin-antagonists of the formulaR.sup.1 -A-B-C-E-F-G-J-K-R.sup.2wherein R.sup.1 represents hydrogen, C.sub.1 -C.sub.4 -alkanoyl which can be substituted by mercapto, hydroxyphenyl, (4-benzoyl)phenoxy or represents (4-benzoyl)benzoyl-Lys; A represents D-Arg or D-Lys or stands for a direct bond; B represents Arg which can be substituted by NO.sub.2 or toluol-4-sulfonyl or represents Lys which can be substituted by toluol-4-sulfonyl or CO--NH--C.sub.6 H.sub.5, or stands for a direct bond; C represents Hyp-Pro-Gly, Pro-Hyp-Gly, Pro-Pro-Gly or dehydroPro-Hyp-Gly; E represents Thi, Phe, Leu or Cha; F represents Ser or Cys; G represents D-Tic, D-Phe or D-Hyp substituted by C.sub.1 -C.sub.4 -alkoxy; J represents Tic, Aoc or Oic; K represents Arg or Ahx or stands for a direct bond; R.sup.

Abstract: The present invention pertains to modified bradykinin antagonist peptides of the formula X-A.sup.0 -B.sup.1 -C.sup.2 -D.sup.3 -E.sup.4 -F.sup.5 -G.sup.6 -H.sup.7 -J.sup.8 -K.sup.9, where at least one of F.sup.5, H.sup.7 and J.sup.8 is an indane substituted amino acids.

Abstract: Peptides of the formula IA-B-C-E-F-K-P-G-M-F'-I (I),wherein the terms A, B, C, E, F, K, P, G, M, F', and I are defined in the specification, have bradykinin antagonist action. Their therapeutic utility includes all pathological states which are mediated, caused or supported by bradykinin and bradykinin-related peptides.