Abstract: The instant invention provides two-chain IGF-1 superagonists which are derivatives of the naturally occurring single-chain IGF-1 having an abbreviated C domain. The invention also provides synthetic and semi-synthetic DNA sequences, recombinant DNA vectors and transformed host cells useful in the recombinant production of these analogs. The invention also provides pharmaceutical formulations comprising these IGF-1 analogs. The invention also provides methods of using these analogs in a variety of therapeutic applications. The instant invention provides IGF-1 analogs of the formula:BC.sup.n,A (1)wherein:B is the B domain of IGF-1 or a functional analog thereof,C is the C domain of IGF-1 or a functional analog thereof,n is the number of amino acids in the C domain and is from about 6 to about 12, andA is the A domain of IGF-1 or a functional analog thereof.

Abstract: The present invention provides a novel synthesis of the compounds of Formula (I): ##STR1## The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereoselective.

Abstract: The present invention discloses a process of preparing a crystalline alkali metal or ammonium salt of Lys.sup.B28 Pro.sup.B29 -human insulin. 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: The present invention provides derivatives of tissue plasminogen activator that lack the Finger, Growth Factor and Kringle 1 domains and comprise a Kringle 2 domain that is monoglycosylated at a site other than that of t-PA. Using recombinant DNA techniques, an alternate glycosylation sequence is provided within the Kringle 2 domain of these t-PA derivatives. This alternate glycosylation consensus sequence, as well as the glycosylation consensus sequence within the Serine Protease domain, is glycosylated upon the expression and secretion of these molecules from eucaryotic host cells. Thus, a homogeneous population of diglycosylated t-PA derivatives that lack the Finger, Growth Factor and Kringle 1 domains is produced.

Abstract: Echinocandin B deacylase is purified to near homogeneity from Actinoplanes utahensis by a process comprising, in order, extracting the soluble enzyme, heating to 60.degree. C., hydrophobic interaction chromatography, (NH.sub.4).sub.2 SO.sub.4 fractionation, gel filtration, cation exchange chromatography, dye-ligand chromatography, gel filtration, and cation-exchange chromatography.

Abstract: A method for removing dipeptides from the amino terminus of precursor polypeptides to produce a polypeptide product is presented which comprises contacting the precursor polypeptide for sufficient time to remove the dipeptide with an immobilized dipeptidylaminopeptidase (dDAP) from the slime mold, Dictyostelium discoideum, which has a mass of about 225 kilodaltons and a pH optimum of about 3.5. The precursor polypeptides may be made recombinantly and may be analogs of naturally occurring polypeptides.

Abstract: N-terminal truncated forms of glucagon like insulinotropic peptide (GLP-1) and analogs thereof are provided. The claimed polypeptides promote glucose uptake by cells but do not stimulate insulin expression or secretion. The invention also provides methods for treating diabetes and pharmaceutical formulations comprising the claimed polypeptides.

Abstract: A dipeptidylaminopeptidase (dDAP enzyme) and a method for isolating it from the culture medium of the cellular slime mold, Dictyostelium discoideum have been presented. The isolated dDAP enzyme has a pH optimum of about 3.5 and a mass of about 225 kDA. The dDAP enzyme has an activity which is somewhat similar to both DAP-I and DAP-III from this organism. Methods for using the dDAP enzyme to remove dipeptides from the N-terminus of recombinantly produced precursor proteins or peptides are also presented.

Abstract: A method for removing dipeptides from the amino terminus of precursor polypeptides to produce a polypeptide product is presented which comprises contacting the precursor polypeptide for sufficient time to remove the dipeptide with a dipeptidylaminopeptidase (dDAP) from the slime mold, Dictyostelium descoideum, which has a mass of about 225 kilodaltons and a pH optimum of about 3.5. The precursor polypeptides may be made recombinantly and may be analogs of naturally occurring polypeptides.

Abstract: Analogs of human insulin containing an aspartic acid at position 1 of the B chain (Asp.sup.B1), and optionally, having a gln modification at position 13 (Gln.sup.B13), display modified physico-chemical and pharmacokinetic properties which enable them to be long acting. These analogs are useful in the treatment of hyperglycemia because they are soluble and display an increased tendency to self-associate.

Abstract: The present invention provides a novel synthesis of the compounds of Formula (I): ##STR1## The compounds are produced in high yield and without utilizing expensive chromatographic separations. The synthesis is particularly advantageous because it is stereoselective.

Abstract: The present invention is based of the discovery of two modified forms of human platelet factor-4, herein named MPF-4 and CPF-4, which were isolated from serum free culture medium of lipopolysaccharide-stimulated peripheral blood leukocytes. Amino acid sequence determination revealed that MPF-4 shares homology with platelet factor-4 beginning at N-terminal residue 17. CPF-4 consists of MPF-4 disulfide bonded to the 16 N-terminal residues of platelet factor-4. Both MPF-4 and CPF-4 are potent inhibitors of endothelial cell proliferation, approximately 10-100 fold more potent than native or recombinant platelet factor-4, making them useful in the treatment of angiogenic diseases.

Abstract: The present invention is based of the discovery of two modified forms of human platelet factor-4, herein named MPF-4 and CPF-4, which were isolated from serum free culture medium of lipopolysaccharide-stimulated peripheral blood leukocytes. Amino acid sequence determination revealed that MPF-4 shares homology with platelet factor-4 beginning at N-terminal residue 17. CPF-4 consists of MPF-4 disulfide bonded to the 16 N-terminal residues of platelet factor-4. Both MPF-4 and CPF-4 are potent inhibitors of endothelial cell proliferation, approximately 10-100 fold more potent than native or recombinant platelet factor-4, making them useful in the treatment of angiogenic diseases.

Abstract: Glucagon-like insulinotropic peptide (GLP-1(7-37)) analogs and derivatives are disclosed. The analogs include amino acid substitutions, amino and carboxyl terminal modifications, and C.sub.6 -C.sub.10 acylations.

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: The present invention is a method for minimizing and containing injury caused when tissue is subject to ischemia and reperfusion. The method comprises administering certain derivatized tripeptide arginal compounds concurent with, or immediately after, reestablishing blood flow to the ischemic tissue. The method is particularly useful for minimizing and containing damage to the heart during evolving myocardial infarction.

Abstract: This disclosure relates to new compounds and to a process for the controlled conversion of such compounds to produce a Protein that comprises an amino acid sequence which is useful as a precursor to human insulin or to a modified human insulin, the amino terminus portion of which sequence does not define a cathepsin C dipeptide removal stop point. The compounds have the formula Met-Y-Protein in which Y is Tyr or Arg.

Abstract: The present invention comprises novel recombinant DNA compounds which encode the .about.40,000 dalton adenocarcinoma antigen recognized by monoclonal antibody KS 1/4. Eukaryotic and prokaryotic expression vectors have been constructed that comprise novel KSA-encoding DNA and drive expression of KSA when transformed into an appropriate host cell. The novel expression vectors can be used to produce KSA derivatives, such as non-glycosylated KSA, and to produce KSA precursors, such as nascent KSA, and to produce subfragments of KSA. The recombinant-produced KSA is useful for the diagnosis, prognosis and treatment of disease states including adenocarcinomas of the lung, prostate, breast, ovary and colon/rectum; and for the creation of novel antibodies for treatment or diagnosis of the above.

Abstract: The invention includes recombinant DNA compounds, vectors and methods useful for expressing an exceptionally rare, human, cytosolic phospholipase A.sub.2 (cPLA.sub.2) enzyme. The invention also includes a method for screening compounds to identify inhibitors of cPLA.sub.2 which is believed to partake in several disease processes.

Abstract: The invention concerns compounds and methods for the recombinant production of a homogeneous population of tissue plasminogen activator molecules and derivatives thereof through the use of heterologous propeptide regions that are uniformly cleaved upon secretion from the host cell.