Synthesis of an insulin-like compound consisting of the B chain of insulin and an A chain corresponding to the A and D domains of human insulin-like growth factor I

Abstract

We report the synthesis and biological evaluation of a two-chain, disulfide-linked, insulin-like compound in which the A chain amino acid sequence corresponds to that of the A- and D-domains of human insulin-like growth factor I (IGF-I), and the B chain is that of bovine insulin. The compound displays reduced insulin-like activity, but considerably increased growth-promoting activity relative to insulin, and is not recognized by IGF carrier proteins. These data confirm some of our earlier conclusions regarding the role of the A-, B- and D-domains in the expression of the biological profile of IGF-I: The A-domain, but not the B- or D-domain is associated with the growth-promoting activity of IGF-I; the B-domain, but not the A- or D-domain, contains determinants for the recognition of IGF carrier proteins; and the D-domain acts to supress insulin-like activity in IGF-I.