Abstract: Analogs of the decapeptide GnRH which include two significantly modified amino acids at positions 5 and 6 inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. Particularly effective peptides which are soluble in water at physiologic pH and which have a low tendency to gel when administered in vivo have the following formula:Ac-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(Q.sub.1)(3-amino-1,2,4 triazole)-D-Aph(Q.sub.2)(3-amino 1,2,4-triazole)-Leu-Lys (isopropyl)-Pro-D-Ala-NH.sub.2,where Q.sub.1 and Q.sub.2 are amino acids, such as Gly, .beta.-Ala, Ala, D-Ala, Ser, Aib, Ahx and Gab. Examples of other GnRH antagonists includeAc-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(Atz)-D-Aph(Ac)-Leu-Lys(isopropyl )-Pro-D-Ala-NH.sub.2,Ac-.beta.

Abstract: The present invention discloses a process of preparing a crystalline insulin analog. The process is useful in the purification and manufacture of Lys.sup.B28 Pro.sup.B29 -human insulin. Lys.sup.B28 Pro.sup.B29 -human insulin is useful in the treatment of diabetes.

Abstract: Novel peptide derivatives having RGD as a basic structure were found which have a platelet aggregation-inhibiting action, blood coagulation-inhibiting action and cell adhesion-inhibiting action.Utlizing these effects of the peptide derivatives, the following agents which comprise the peptides as active ingredients were provided: platelet aggregation-inhibiting agents that are effective in thrombolus during and after the treatment of thrombolysis and thromboembolism and that can further prevent reobstruction and cardiac infarction; blood coagulation-inhibiting agents that can inhibit blood coagulation which is the main cause of thrombus formation during extracorporeal circulation; cell adhesion-inhibiting agents; tumor metastasis-inhibiting agents; and agents for protecting platelet preparations for blood transfusion.

Abstract: A peptide derivative of the formula: ##STR1## is a novel compound having antagonism against three endothelin isopeptides. A 2-cyanotryptophan or a protected compound thereof, is an intermediate for the preparation of the endothelin antagonist.

Abstract: High affinity binding of nidogen to laminin is mediated by an EGF-like repeat .gamma.1III4 of the mouse laminin .gamma.1 chain and has now been restricted to two short non-contiguous regions of its 56 residue sequence by use of synthetic peptides and recombinant mutants. Disulfide loop a,b of the repeat and a modified loop a,c could completely inhibit binding, with a 5,000-fold or 300-fold reduced affinity, respectively. Synthetic loops c and d lacked inhibitory activity. Some binding contribution of Try819 in loop c was, however, shown by mutation and side chain modification. Together with studies of loop chimeras, this indicated a distinct cooperativity between the two binding sites. The major binding site of loop a was localized to the heptapeptide NIDPNAV (position 798-804). A change of Asp800 to Asn or Ala803 to Val caused a strong reduction in binding activity, while only small effects were observed for the changes Pro801 to Gln and Ile799 to Val.

Abstract: The present invention as directed to a compound which comprises an endothelin antagonist polypeptide that is at least 40% homologous to an endothelin active peptide, consisting of Et-1, Et-2, Et-3, SC, SA and SB and has the formula: ##STR1## and pharmaceutically acceptable salts.

Abstract: This invention relates to human insulin analogs (tri-arg insulins) and includes two enzymatic methods for producing tri-arg insulins. These compounds can be formulated as a soluble entity up to pH 6.1 and have prolonged hypoglycemic activity. Tri-arg insulins have the basic structure of natural human insulin plus three additional arginine residues. Two of the three additional Arg residues are located in tandem at the carboxy terminus of the insulin B-chain, and the third Arg residue is located at the amino terminus of the insulin A-chain. Tri-arg insulin analogs, having certain amino acid substitutions at the B3, B10 and A21 positions, are within the instant invention.

Abstract: A class of potent LHRH decapeptide antagonists possess N-alkylated aminoacyl residues where the side-chain portion of the residue is a 4-(substimtedamino)phenylalanyl, 4-(substituted-amino)cyclohexylalanyl, or .OMEGA.-(substitutedamino)alkyl group, and additionally the aminoacyl residues at position 5 are N-alkylated on the nitrogen atom of the peptide backbone.

Abstract: The invention concerns peptides which have a partial sequence of lipoprotein (a) as well as their use for the purification of antibodies by means of affinity chromatography, as an immunogen for the production of antibodies and as a standard in an immunological test or as a competitive hapten in an agglutination test.

Abstract: Radionuclide chelating compounds are provided for conjugation to targetting molecules such as proteins, peptides or antibodies. The resulting labelled targetting molecules may be used in diagnosis and therapy.

Abstract: Glucagon analogs characterized principally by the removal or replacement of the 9-aspartic acid residue or its replacement with another amino acid residue together with replacement of the 16-serine residue and possible replacement of the 11-serine residue and 21-aspartic acid residue with or without a histidine at the amino terminal are useful adjuncts to insulin therapy.

Abstract: Hemoglobin-containing solutions containing polyalkyene oxide-conjugated hemoglobin having a molecular weight greater than about 85,000 daltons and a degree of substitution of at least five polyalkylene oxide conjugates per hemoglobin molecule are described that are not associated with hemoglobinuria in mammals. A method of simultaneously fractionating and purifying polyalkylene oxide-conjugated hemoglobins is also disclosed.

Abstract: Proteins having substantially the same biological activity as PDGF are provided. In one aspect, a protein homodimer having two polypeptide chains is disclosed, each of the chains being a mosaic of amino acid sequences substantially identical to portions of the A- and B-chains of PDGF, the protein being chemotactic or mitogenic for fibroblasts. Therapeutic compositions comprising such proteins in combination with a physiologically acceptable carrier or diluent are also provided. Such therapeutic compositions may be used within methods for enhancing the wound-healing process in warm-blooded animals.

Abstract: The present invention discloses a human insulin analog hexamer complex and formulations. More specifically, the present invention relates to various parenteral formulations, which comprise: human insulin analogs in a hexamer conformation, zinc ions, and at least three molecules of a phenolic derivative selected from the group consisting of m-cresol, phenol, or a mixture of m-cresol and phenol. The formulation provides a rapid onset of action.

Abstract: A process is described for obtaining proinsulin possessing correctly linked cystine bridges from a corresponding proinsulin amino acid chain in the presence of mercaptan and chaotropic auxiliary agents and at a pH of 10 to 11, as well as its direct isolation from the reaction mixture using hydrophobic adsorber resins.

Abstract: Biologically active amphiphilic peptides including one of the following basic structures: I. R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.1 --R.sub.1 ; II. R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 ; III. R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.3 ; IV. R.sub.1 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.4 ; V. R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.3 ; or VI. R.sub.1 --R.sub. 1 --R.sub.3 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.1 --R.sub.2 --R.sub.2 --R.sub.1.R.sub.1 is a hydrophobic amino acid and R.sub.

Abstract: A process for the production of an amorphous monospheric form of insulin derivatives is described, wherein the insulin derivative is dissolved in an n-propanol/buffer mixture at a pH of 4.5 to 6.5, an n-propanol content of more than 13% relative to water is established and the resulting solution is subsequently diluted with water.

Abstract: This invention relates to an intraocular irrigating composition containing a compound of the following formula or a pharmacologically acceptable salt thereof ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represents a hydrogen atom or a methyl group.The glutathione derivative contained in the intraocular irrigating solution of this invention is not only effective in protecting the intraocular tissues on the occasion of ophthalmic surgery but effectively inhibits precipitation of the calcium contained. Therefore, the intraocular irrigating solution of this invention is very stable and can be used with advantage in various kinds of ophthalmic surgery such as cataract surgery and transplantation of the cornea, iris and vitreous body.

Abstract: The invention relates to the use of IGF-1 for the manufacture of a medicament for treatment of Type 1 diabetes mellitus. the medicament comprising a subcutaneous dose not greater than needed to achieve an IGF-1 serum level characteristic for healthy individuals i.e. a physiological replacement of serum IGF-1. This treatment would be especially valuable for the treatment of children or adolescents with Type 1 diabetes mellitus and could lead to improvements in their pubertal growth.

Abstract: The present invention discloses various parenteral pharmaceutical formulations, which comprise: a monomeric insulin analog, zinc, protamine, and phenolic derivative. The analog formulations provide a prolonged duration of action. A process for preparing insulin analog-protamine formulations is also described.