title: A synthetic route to human insulin using isoacyl peptides.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 (USA). liufx@lilly.com.
authors.forename: Fa
authors.initials: F
authors.lastname: Liu
authors.forename: Ethan Y
authors.initials: EY
authors.lastname: Luo
authors.forename: David B
authors.initials: DB
authors.lastname: Flora
authors.forename: Adam R
authors.initials: AR
authors.lastname: Mezo
mesh_terms: D006801:Humans; D007328:Insulin / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding
chemical_list: D007328:Insulin; D010455:Peptides
keywords: insulin; peptides; protein folding; proteins; synthetic methods