Semi-synthesis of human insulin by trypsin-catalysed replacement of Ala-B30 by Thr in porcine insulin

Abstract

HUMAN insulin differs from porcine insulin by a single amino acid (Thr instead of Ala) at the C-terminal residue of the B-chain. Inouye et al.¹ have established a procedure for the semi-synthesis of human insulin, in which trypsin is used as a catalyst for the coupling of desoctapeptide-(B23–B30)-insulin (DOI) with a synthetic octapeptide corresponding to positions B23–B30 of human insulin. DOI was prepared by tryptic digestion of porcine insulin. The enzymatic method has many advantages, in particular, better yields and simple operation, over the chemical methods originally used by Ruttenberg² and Obermeier and Geiger³. Here we report a more simple and economical method for the semi-synthesis, in which trypsin can catalyse the coupling between desalanine-B30-insulin (DAI) and Thr-OBu^t to generate human insulin in good yield.