Design and Folding of [Glu A4 (O β Thr B30 )]Insulin (“Ester Insulin”): A Minimal Proinsulin Surrogate that Can Be Chemically Converted into Human Insulin

Insulin folding: An ester-linked polypeptide proinsulin surrogate folded efficiently with concomitant disulfide bond formation, and saponification gave native insulin having full biological activity. This strategy overcomes the low yield combination of individual insulin A and B chains, and provides a simple and effective approach to the total chemical synthesis of human insulin and its analogues.