Ferricyanide-Promoted Oxidative Activation and Ligation of Protein Thioacids in Neutral Aqueous Media  

作　　者：Guo-Chao Chu Lu-Jun Liang Rui Zhao Yan-Yan Guo Chun-Tong Li Chong Zuo Huasong Ai Xiao Hua Zi-Chen Li Yi-Ming Li Lei Liu 

机构地区：[1]NewCornerstone Science Laboratory,Tsinghua-Peking Center for Life Sciences,Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology,Center for Synthetic and Systems Biology,Department of Chemistry,Tsinghua University,Beijing 100084 [2]School of Food and Biological Engineering,Hefei University of Technology,Hefei 230009 [3]Center for BioAnalytical Chemistry,Hefei National Laboratory of Physical Science at Microscale,University of Science and Technology of China,Hefei 230026 [4]Department of Chemistry,University of Science and Technology of China,Hefei 230026

出　　处：《CCS Chemistry》2024年第8期2031-2043,共13页中国化学会会刊（英文）

基　　金：supported by the National Key R&D Program of China(grant no.2022YFC3401500);the National Natural Science Foundation of China(grant nos.22137005,92253302,and 22227810 for L.Liu,21877024 for Y.M.Li);the China Postdoctoral Science Foundation(grant nos.2021M691747 for G.C.Chu,2021M701862 and 2022T150347 for L.J.Liang);New Cornerstone Science Foundation.

摘　　要：Ferricyanide-promoted oxidative activation of Nacylatedα-aminothioacids for amide bond formation withα-aminonitriles was recently shown to be a plausible pathway for prebiotic peptide synthesis.Herein we describe the finding that by adding sodium azide and thiols,ferricyanide oxidation can elicit highly efficient and clean conversion of fully unprotected peptide or protein thioacids in neutral aqueous media to the corresponding thioesters.This transformation enables the development of ferricyanide-promoted thioacid-based native chemical ligation(NCL)as a new redox-based method for chemical protein synthesis,which does not need to change pH and is therefore operationally easy for ligation at small scales.The effectiveness of the ferricyanide-promoted thioacid-based NCL was illustrated by synthesis of an ISG15-modified MDA5 segment under nondenaturing conditions and synthesis of an acetylated ubiquitin(Ub)-modified histone H2A through an N-to-C sequential ligation.This work broadens the concept of on-demand oxidative activation strategy for protein ligation and provides a new useful supplement to the repertoire of methods for chemical protein synthesis,particularly for studies on proteins carrying Ub family modifications.

关 键 词：chemical protein synthesis protein thioacid ferricyanide oxidation native chemical ligation ubiquitin family modifications 

分 类 号：O62[理学—有机化学]