Triple Function of 4‐Mercaptophenylacetic Acid Promotes One‐Pot Multiple Peptide Ligation,Angewandte Chemie International Edition

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Triple Function of 4‐Mercaptophenylacetic Acid Promotes One‐Pot Multiple Peptide Ligation
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2018-11-14 , DOI: 10.1002/anie.201809765
Naoki Kamo ₁ , Gosuke Hayashi ₁ , Akimitsu Okamoto _{1,

2}

Affiliation

One‐pot multiple peptide ligation is a key technology to improve the efficiency of chemical protein synthesis. One‐pot repetitive peptide ligation requires a cycle of three steps: peptide ligation, removal of a protecting group, and inactivation of the deprotection reagent. However, previous strategies are not sufficient because of harsh deprotection conditions, slow deprotection rates, and difficulty in quenching the deprotection reagent. To address these issues, we developed a rapid, efficient deprotection and subsequent quenching strategy using an allyloxycarbonyl group to protect the N‐terminal cysteine residue. 4‐Mercaptophenylacetic acid (MPAA), a thiol additive for native chemical ligation, functioned not only as a scavenger for π‐allyl palladium complexes, but also as a quencher of palladium(0) complexes. By utilizing the multifunctionality of MPAA, we carried out a one‐pot five‐segment ligation to afford histone H2AX (142 amino acids), which was isolated in 59 % yield.

中文翻译：

4-巯基苯乙酸的三功能促进单电位多肽连接

单罐多肽连接是提高化学蛋白质合成效率的关键技术。一锅式重复肽连接需要三个步骤的循环：肽连接，保护基的去除和去保护剂的失活。然而，由于苛刻的脱保护条件，缓慢的脱保护速率以及难以淬灭脱保护剂的原因，先前的策略是不够的。为了解决这些问题，我们开发了一种快速，有效的脱保护和后续的淬灭策略，使用烯丙氧基羰基保护了N端半胱氨酸残基。4-巯基苯乙酸（MPAA）是用于天然化学连接的硫醇添加剂，不仅用作π-烯丙基钯配合物的清除剂，而且还用作钯（0）配合物的猝灭剂。

更新日期：2018-11-14

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