Biomimetic Synthesis of Insulin Enabled by Oxime Ligation and Traceless “C-Peptide” Chemical Excision

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• 作者：Kishore Thalluri ; Binbin Kou ; Vasily Gelfanov ; John P. Mayer ; Fa LiuRichard D. DiMarchi
• 刊名：Organic Letters
• 出版年：2017
• 出版时间：February 3, 2017
• 年：2017
• 卷：19
• 期：3
• 页码：706-709
• 全文大小：356K
• ISSN：1523-7052

文摘

For decades, insulin has represented a preeminent synthetic target. Recently introduced “biomimetic” strategies based on convertible single-chain precursors require incorporation of a chemical linker or a unique proteolytic site, which limits their practicality. In this approach the A- and B-chains are linked by two sequential oxime ligations followed by disulfide bond formation under redox conditions and linker excision by diketopiperazine (DKP) formation and ester hydrolysis, yielding native two-chain insulin. The method is expected to be applicable to any member of the insulin superfamily.