Collect. Czech. Chem. Commun. 1988, 53, 2920-2935

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

Gerald P. Schwartz, G. Thompson Burke, Maqsood Sheikh, Lin Zong and Panayotis G. Katsoyannis

Department of Biochemistry, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029, U.S.A.


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.