A Glycosidic-Bond-Based Mass-Spectrometry-Cleavable Cross-linker Enables In Vivo Cross-linking for Protein Complex Analysis

被引：16

作者：

Chen, Jing ^{[1
,2
]}

Zhao, Qun ^{[1
]}

Gao, Hang ^{[1
,3
]}

Zhao, Lili ^{[1
,3
]}

Chu, Huiying ^{[4
]}

Shan, Yichu ^{[1
]}

Liang, Zhen ^{[1
]}

Zhang, Yukui ^{[1
]}

Zhang, Lihua ^{[1
]}

机构：

[1] Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Labratory Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Peoples R China

[2] Univ Sci & Technol China, Sch Chem & Mat Sci, 96 Jinzhai Rd, Hefei 230026, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100039, Peoples R China

[4] Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, 457 Zhongshan Rd, Dalian 116023, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2023年 / 62卷 / 24期

关键词：

Cleavage Reactions; Glycosidics; Mass Spectrometry; Protein Structures; Protein-Protein Interactions; IDENTIFICATION; PROTEOMICS; DISCOVERY; WORKFLOW; GLYCANS;

D O I：

10.1002/anie.202212860

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Chemical cross-linking mass spectrometry (CXMS) has emerged as a powerful technology to analyze protein complexes. However, the progress of in vivo CXMS studies has been limited by cross-linking biocompatibility and data analysis. Herein, a glycosidic bond-based MS-cleavable cross-linker of trehalose disuccinimidyl ester (TDS) was designed and synthesized, which was fragmented in MS under CID/HCD to simplify the cross-linked peptides into conventional single peptides via selective cleavage between glycosidic and peptide bonds under individual MS collision energy. Consequently, the cross-linking identification accuracy and throughput were significantly enhanced, and the popular MS mode of stepped HCD was allowed. In addition, TDS showed proper cell-penetrating properties while being highly water-soluble, making it non-DMSO dependent during solubilization. Collectively, TDS provides a promising toolkit for CXMS characterization of living systems with high biocompatibility and accuracy.

引用

页数：9

共 37 条

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