Thiolation and disulphide cross-linking of insulin to form macromolecules of potential therapeutic value.

Abstract

Macromolecules have been prepared containing native insulin carried by a modified insulin skeleton made by partially thiolating the insulin hexamer and forming intermolecular cross-links through disulphide bridges. Oxidation of partially thiolated insulin (0.5-0.7 SH group/mole), formed by reacting insulin with AHTL, with, (a) potassium ferricyanide, (b) Cu++-oxygen gave water soluble macromolecules containing 20-26 and 410-708 monomer units respectively which had rod-random coil shape (light scattering). The larger molecules formed by (b) contained 8g-atom CU++/hexamer unit and insulin. The insulin was firmly bound within the marcomolecules and was probably bound within an insulin-modified insulin hexamer through coordination to copper.