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De Novo Chemoenzymatic Assembly of Complex Sulfated N-Glycans to Comprehensively Profile the Ligand Binding of Human Siglecs

文献类型：期刊论文

作者Ma, Shengzhou3,4; Zhang, Jiabin1,2,4; Wei, Fangyu2,3,4; Tian, Xiao1; Tian, Yinping3,4; Wen, Liuqing2,3,4
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2025-09-24
卷号147期号:38页码:35042-35054
ISSN号0002-7863
DOI10.1021/jacs.5c11949
通讯作者Wen, Liuqing(lwen@simm.ac.cn)
英文摘要The Siglec family represents one of the major classes of human glycan-binding proteins (GBPs) that regulates a broad range of biological processes through engagement with their glycan ligands. Human Siglecs have attracted a great deal of attention in recent years, as they are regarded as new immune checkpoints. The disruption of Siglec-sialoglycan interactions represents a promising next-generation strategy for cancer immunotherapy. In addition to the sialic acid moiety, it has been well established that glycan sulfation plays an essential role in the ligand binding of human Siglecs. Therefore, there is an urgent need to thoroughly understand the subtle differences in the glycan scaffolds and sulfation patterns that govern Siglec binding. N-Glycans are the most abundant class of glycans occurring in living cells, while sulfation is the most widespread postglycosylation modification of N-glycans, indicating that sulfated N-glycans serve as key ligands for human Siglecs. However, the synthetic generation of large libraries of complex sulfated N-glycans is impractical as sulfation introduces additional challenges to the already demanding process of N-glycan synthesis. Herein, we describe a de novo chemoenzymatic approach for the efficient preparation of complex sulfated N-glycans. Using this approach, a comprehensive 72-member library of sulfated N-glycans encompassing the most typical complex structures was successfully prepared. With the well-defined library (comprising 72 sulfated N-glycans and 26 nonsulfated controls), we systematically investigated the binding activities of all human Siglecs. Beyond the synthetic breakthroughs, this work provides the most comprehensive profile to date for understanding how sulfation patterns and N-glycan scaffolds affect Siglec ligand binding, which will have an immediate impact on the development of Siglec-targeted immunotherapy strategies.
WOS关键词ENZYMATIC-SYNTHESIS ; MAACKIA-AMURENSIS ; ACETYLLACTOSAMINE ; RECEPTOR ; ALPHA-2,6-SIALYLTRANSFERASE ; SIALYLTRANSFERASE ; OLIGOSACCHARIDES ; SPECIFICITY ; AFFINITY ; REVEALS
资助项目National Natural Science Foundation of China[22207113] ; National Natural Science Foundation of China[CASSHB-QNPD-2023-018] ; Talent Plan of Shanghai Branch, Chinese Academy of Sciences[XDB1060000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[SKLCB-2025-04] ; State Key Laboratory of Chemical Biology ; Shanghai Municipal Science and Technology Major Project[2024M753373] ; China Postdoctoral Science Foundation
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001571630200001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/321456]  
专题中国科学院上海药物研究所
通讯作者Wen, Liuqing
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Shengzhou,Zhang, Jiabin,Wei, Fangyu,et al. De Novo Chemoenzymatic Assembly of Complex Sulfated N-Glycans to Comprehensively Profile the Ligand Binding of Human Siglecs[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2025,147(38):35042-35054.
APA Ma, Shengzhou,Zhang, Jiabin,Wei, Fangyu,Tian, Xiao,Tian, Yinping,&Wen, Liuqing.(2025).De Novo Chemoenzymatic Assembly of Complex Sulfated N-Glycans to Comprehensively Profile the Ligand Binding of Human Siglecs.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,147(38),35042-35054.
MLA Ma, Shengzhou,et al."De Novo Chemoenzymatic Assembly of Complex Sulfated N-Glycans to Comprehensively Profile the Ligand Binding of Human Siglecs".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147.38(2025):35042-35054.

入库方式： OAI收割

来源：上海药物研究所

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