An improved installation of 2-hydroxy-4-methoxybenzyl(iHmb)method for chemical protein synthesis

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外文摘要：The 2-hydroxy-4-methoxybenzyl(Hmb)backbone modification can prevent amide bond-mediated side-reactions(e.g.,aspartimide formation,peptide aggregation)by installing the removable Hmb group into a peptide bond,thus improving the synthesis of long and challenging peptides and proteins.However,its use is largely precluded by the limited Hmb's installation sites.In this report,an improved installa-tion of Hmb(iHmb)method was developed to achieve the flexible installation and the convenient re-moval of Hmb.The iHmb method involves two critical steps:(1)oxidative diazotization of the readily in-stalled 2-hydroxy-4-methoxy-5-amino-benzyl(Hmab)to give 2-hydroxy-4-methoxy-5-diazonium-benzyl(Hmdab)by combining soamyl nitrite(1AN)/HBF4,and(2)reductive elimination of Hmdab to give the de-sired Hmb by 1,2-ethanedithiol(EDT).The iHmb method enables the installation of Hmb at any primary amino acid including the highly sterically hindered amino acids(e.g.,valine and isoleucine).The practical-ity and utility of the iHmb method was demonstrated by one-shot solid-phase synthesis of a challenging aspartimide-prone peptide,the mirror-image version of a hydrophobic peptide and a long-chain peptide up to 76-residue.Furthermore,the iHmb method can be utilized to facilitate chemical protein ligation,as exemplified by the synthesis of the single-spanning membrane protein sarcolipin.The iHmb method expands the toolkit for peptide synthesis and ligation and facilitates the preparation of peptides/proteins.

外文关键词：

Chemical protein synthesisSolid-phase peptide synthesisRemovable backbone modification2-Hydroxy-4-methoxybenzyl(Hmb)groupAspartimide-prone peptidesDifficult peptidesMembrane proteins

作者：

Ying Li、Long-Jie Wang、Yong-Kang Zhou、Jun Liang、Bin Xiao、Ji-Shen Zheng

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作者单位：

The First Affiliated Hospital of USTC,MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China

Department of Chemistry,University of Science and Technology of China,Hefei 230027,China

基金：

国家重点研发计划国家自然科学基金国家自然科学基金Collaborative Innovation Program of Hefei Science Center,CAS

项目编号：

2019YFA070690022022703221771082022HSC-CIP013

出版年：

2024

DOI：

10.1016/j.cclet.2023.109033

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCD

影响因子：0.771

ISSN：1001-8417

年,卷(期)：2024.35(5)

参考文献量48