Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 (USA).
Angew Chem Int Ed Engl. 2014 Apr 7;53(15):3983-7. doi: 10.1002/anie.201310735. Epub 2014 Mar 11.
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.
胰岛素的化学合成一直是一个长期存在的挑战，主要是因为 A 链的恶名昭著的疏水性和由两条链和三个二硫键组成的这个 51 肽激素的复杂拓扑结构。本文报道了一种利用异酰肽方法解决疏水性问题的新合成途径。在 A 链和 B 链中引入异酰二肽片段，极大地改善了它们的制备和纯化，以及链连接中间体的 RP-HPLC 回收率。根据起始纯化的 A 链，新路线提供了 68%的人胰岛素产率，根据用于制备 A 链的树脂的取代，总产率为 24%。据我们所知，这代表了迄今为止报道的最有效的人胰岛素化学合成途径。
