A Synthetic Route to Human Insulin Using Isoacyl Peptides1. Issue 15 (11th March 2014)

• Record Type: Journal Article
• Authors: Liu, Fa; Luo, Ethan Y.; Flora, David B.; Mezo, Adam R.
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 15(2014)
• Page Start: 3983
• Page End: 3987
• Publication Date: 2014-03-11
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201310735
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The chemical synthesis of insulin has been a longstanding challenge, mainly because of the notorious hydrophobicity of the A chain and the complicated topology of this 51‐mer peptide hormone consisting of two chains and three disulfide bonds. Reported herein is a new synthetic route utilizing the isoacyl peptide approach to address the hydrophobicity problems. The incorporation of isoacyl dipeptide segments into both A and B chains greatly improved their preparation and purification, and the RP‐HPLC recovery of the chain ligation intermediates. The new route affords human insulin with a yield of 68 % based on the starting purified A chain and an overall yield of 24 % based on the substitution of the resin used for the preparation of A chain. To the best of our knowledge, this represents the most efficient route of human insulin chemical synthesis reported to date.</p> </abstract>