Direct Identification of a Novel Disulfide Bond Linkage System of New Isolated Isomer (Isomer V) in Recombinantly Produced h-IGF-I

Abstract

Insulin-like growth factor I (IGF-I or somatomedin C) is a serum polypeptide with three intramolecular disulfide bond. In the course of synthesis by the recombinant DNA method, three disulfide bond isomers, all of which have Cys¹⁸-Cys⁶¹ with three combinations of two disulfide bonds formed by Cys⁶, Cys⁴⁷, Cys⁴⁸ and Cys⁵², were identified. Natural type, isomer II, was proved to have a Cys⁶-Cys⁴⁸, Cys¹⁸-Cys⁶¹, Cys⁴⁷-Cys⁵² disulfide bond system. Now, the fourth isomer, isomer V which doesn't have Cys¹⁸-Cys⁶¹ disulfide, has been isolated, and its novel disulfide bond linkage system was identified by a chemical synthetic method. The supposed conformation constrained in 3D structure for isomer V would be discussed for its biological activity.