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

被引：20

作者：

Thalluri, Kishore ^{[1
]}

Kou, Binbin ^{[2
]}

Gelfanov, Vasily ^{[2
]}

Mayer, John P. ^{[2
]}

Liu, Fa ^{[2
]}

DiMarchi, Richard D. ^{[1
]}

机构：

[1] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA

[2] Novo Nordisk Res Ctr Indianapolis, 5225 Explorat Dr, Indianapolis, IN 46241 USA

来源：

ORGANIC LETTERS | 2017年 / 19卷 / 03期

关键词：

ESTER INSULIN;

D O I：

10.1021/acs.orglett.6b03876

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：706 / 709

页数：4

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