A-C-B proinsulin, method of manufacturing and using same, and intermediates in insulin production
First Claim
1. A Polypeptide compound of the formula:
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space="preserve" listing-type="equation">Met.sub.x --A--C--Bwherein;
Met=the amino acid methionine,x=0 or 1,A=the A chain of insulin or a functional derivative thereof,B=the B chain of insulin or a functional derivative thereof,C=the C peptide of insulin or a peptide of the formula;
space="preserve" listing-type="equation">X.sub.1 --X.sub.2 --P--X.sub.3 --X.sub.4, wherein;
X1, X2, X3, and X4 are basic amino acids,X1, X2, X3, and X4 are the same or different, and,P is a peptide of from 4 to 35 amino acids which does not contain a cysteine residue,and pharmaceutically acceptable salts thereof.
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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.
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Citations
41 Claims
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1. A Polypeptide compound of the formula:
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space="preserve" listing-type="equation">Met.sub.x --A--C--Bwherein; Met=the amino acid methionine, x=0 or 1, A=the A chain of insulin or a functional derivative thereof, B=the B chain of insulin or a functional derivative thereof, C=the C peptide of insulin or a peptide of the formula;
space="preserve" listing-type="equation">X.sub.1 --X.sub.2 --P--X.sub.3 --X.sub.4,wherein; X1, X2, X3, and X4 are basic amino acids, X1, X2, X3, and X4 are the same or different, and, P is a peptide of from 4 to 35 amino acids which does not contain a cysteine residue, and pharmaceutically acceptable salts thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41)
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40. A method of treating non-insulin dependent diabetes mellitus by administering a pharmaceutically acceptable dose of the compound of formula 1.
Specification