NOVEL DERIVATIVES OF INSULIN, NOVL COMPLEXES, PHARMACEUTIC AGENT AND NOVEL PROINSULINS

摘要

Insulin of formula (I): R1 is H or Phe; R3, Y are genetically encodable amino acids; Z = His or a peptide chain of 2-35 genetically encodable amino acids including 1-5 His residues; A2-A20 (not shown) correspond to the amino acid sequence of the A chain of human insulin, an animal insulin or an insulin derivative; B2-B29 (not shown) correspond to the amino acid sequence of the B chain of human insulin, an animal insulin or an insulin derivative. Also claimed are: (1) a complex comprising an insulin hexamer and 5-9 zinc atoms per insulin hexamer, where the hexamer consists of six insulin molecules of formula (I); (2) proinsulin of formula (II): R2-R1'-B2-B29-Y-Z1-Gly-A2-A20-R3 (II) R1' = Phe or a covalent bond; R2 = a genetically encodable amino acid or a peptide chain of 2-45 amino acids, and Z1 is a peptide chain of 2-40 genetically encodable amino acids including 1-5 His residues.