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 instant invention provides novel molecules derived from the components of proinsulin using recombinant DNA technology. The invention provides molecules of the formula A--C--B wherein A is the A-chain of an insulin species, B is the B-chain of an insulin species and C is a connecting peptide. These molecules possess insulin-like activity and are useful for the treatment of diabetes mellitus, particularly non-insulin dependent diabetes mellitus. These molecules are also useful for the production of insulin and constitute a novel pathway for the recombinant production of insulin species. The invention provides a method of making insulin proceeding through the compounds of the invention as intermediates. The instant invention further provides recombinant DNA compounds which encode the compounds of the invention.

Abstract: This application discloses a process for reducing methionine sulfoxide residues in peptides and proteins to methionine residues. The process comprises subjecting said peptide or protein to a substantially anhydrous trifluoroacetic acid reaction medium containing from about 0.01M to about 3M of an organic sulfide and from about 0.01M to about 3M of a haloacid selected from the group consisting of hydrochloric acid, hydrobromic acid, and hydroiodic acid.

Abstract: This application describes a process for selectively cleaving a peptide or protein at one or more of its tryptophan residues. The process comprises treating in trifluoroacetic acid said peptide or protein at a concentration of from about 0.05 mM to about 50 mM with an organic sulfoxide at a concentration of from about 0.01M to about 1M, chloride ion at a concentration of from about 0.01M to about 2M, and water at a concentration not in excess of about 10M.