Total chemical synthesis of bivalently modified H3 by improved three-segment native chemical ligation  

作　　者：Yong Zheng Fangming Wu Shenglong Ling Jia-Bin Li Changlin Tian 

机构地区：[1]High Magnetic Field Laboratory,Chinese Academy of Sciences,Hefei 230031,China [2]School of Life Sciences,University of Science and Technology of China,Hefei 230027,China [3]Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China

出　　处：《Chinese Chemical Letters》2020年第5期1267-1270,共4页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.21708036,31470740,U1732161);Anhui Provincial Natural Science Foundation (No.1808085QC63)。

摘　　要：The H3 bivalent modifications of trimethylationat Lys9 and acetylation at Lys18(H3-K9 Me3-K18 Ac) were identified to collectively recruit TRIM33 in the nodal signaling pathway.To understand the underlying mechanism of TRIM33 recruitment,the nucleosome core particles(NCPs) containing full-length H3-K9 Me3-K18 Ac were indispensable samples.Herein we developed a pseudo dipeptide strategy to efficiently prepare peptide segments,facilitating the chemical synthesis of H3-K9 Me3-K18 Ac at a tens of milligram scale.The synthetic H3-K9 Me3-K18 Ac was then examined by CD spectroscopy,which demonstrated a prominent shift compared to recombinant H3.Finally,bivalently modified NCPs were assembled and verified by gel mobility shift assay with good homogeneity.

关 键 词：Chemical protein synthesis Native chemical ligation Histone H3 METHYLATION ACETYLATION Nucleosome core particles 

分 类 号：O629.73[理学—有机化学]