Molecular Weight of Insulin in N,N-Dimethylformamide

Abstract

THE detailed investigations of Sanger and co-workers have established the molecular weight of insulin as some multiple of about 6,000 1. It is not clear, however, whether the fundamental covalently bonded unit is the 6,000 or 12,000 species. (The determination of the positions of the S—S linkages in insulin1 does not establish the fundamental unit as the 6,000 species. The methods of analysis do not preclude the possibility of a staggered arrangement of the S—S linkages such that the 12,000 species is covalently bonded together.) Several workers using a variety of techniques—osmotic pressure, sedimentation and light-scattering—achieved results indicating that the minimum molecular weight of insulin in aqueous solution is 12,000 2. However, other work has indicated a value of 6,000. Harfeneist and Craig3, by counter-current distribution methods in 2-butanol-dichloracetic acid systems, Fredericq4 by sedimentation-diffusion studies in alkaline solutions, and Kupke and Linderstrom-Lang5 by osmotic pressure determinations in aqueous guanidine chloride solutions, have all recently contributed data consistent with the value of 6,000. Osmotic pressure studies of insulin in N,N-dimethylformamide in this laboratory also indicate a molecular weight of 6,000 for the fundamental unit.