Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics
文献类型:期刊论文
作者 | Xu, Zhuojia3,4; Liu, Yating4; Liu, Jialin4; Ma, Wenjing3,4; Zhang, Zhumin4; Chapla, Digantkumar G.2; Wen, Liuqing3,4; Moremen, Kelley W.2; Yi, Wen1; Li, Tiehai3,4 |
刊名 | NATURE CHEMISTRY
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出版日期 | 2024-06-06 |
页码 | 16 |
ISSN号 | 1755-4330 |
DOI | 10.1038/s41557-024-01540-x |
通讯作者 | Li, Tiehai(tiehaili@simm.ac.cn) |
英文摘要 | Ganglioside glycans are ubiquitous and complex biomolecules that are involved in a wide range of biological functions and disease processes. Variations in sialylation and sulfation render the structural complexity and diversity of ganglioside glycans, and influence protein-carbohydrate interactions. Structural and functional insights into the biological roles of these glycans are impeded due to the limited accessibility of well-defined structures. Here we report an integrated chemoenzymatic strategy for expeditious and systematic synthesis of a comprehensive 65-membered ganglioside glycan library covering all possible patterns of sulfation and sialylation. This strategy relies on the streamlined modular assembly of three common sialylated precursors by highly stereoselective iterative sialylation, modular site-specific sulfation through flexible orthogonal protecting-group manipulations and enzymatic-catalysed diversification using three sialyltransferase modules and a galactosidase module. These diverse ganglioside glycans enable exploration into their structure-function relationships using high-throughput glycan microarray technology, which reveals that different patterns of sulfation and sialylation on these glycans mediate their unique binding specificities. Deciphering the sulfation and sialylation codes of ganglioside glycans is impeded by the limited accessibility of well-defined structures. Now, an integrated chemoenzymatic strategy has been developed for efficient synthesis of a comprehensive 65-membered ganglioside glycan library, enabling an extensive exploration into their structure-function relationships using glycan microarray technology. |
WOS关键词 | MYELIN-ASSOCIATED GLYCOPROTEIN ; ALPHA-SERIES GANGLIOSIDES ; STEREOSELECTIVE-SYNTHESIS ; NEURAL SIGLECS ; BINDING ; ACID ; GLYCOSPHINGOLIPIDS ; LIGANDS ; TETRASACCHARIDE ; IDENTIFICATION |
资助项目 | National Natural Science Foundation of China (National Science Foundation of China)[22077130] ; National Natural Science Foundation of China (National Science Foundation of China)[22377134] ; National Natural Science Foundation of China (National Science Foundation of China)[22325704] ; National Natural Science Foundation of China (National Science Foundation of China)[92353303] ; National Natural Science Foundation of China ; Shanghai Municipal Science and Technology Major Project ; Chinese Academy of Sciences Pioneer Talent Program[20ZR1467900] ; Science and Technology Commission of Shanghai Municipality |
WOS研究方向 | Chemistry |
语种 | 英语 |
WOS记录号 | WOS:001239912700002 |
出版者 | NATURE PORTFOLIO |
源URL | [http://119.78.100.183/handle/2S10ELR8/311588] ![]() |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Li, Tiehai |
作者单位 | 1.Zhejiang Univ, Coll Life Sci, Hangzhou, Zhejiang, Peoples R China 2.Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30605 USA 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, State Key Lab Chem Biol, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Xu, Zhuojia,Liu, Yating,Liu, Jialin,et al. Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics[J]. NATURE CHEMISTRY,2024:16. |
APA | Xu, Zhuojia.,Liu, Yating.,Liu, Jialin.,Ma, Wenjing.,Zhang, Zhumin.,...&Li, Tiehai.(2024).Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics.NATURE CHEMISTRY,16. |
MLA | Xu, Zhuojia,et al."Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics".NATURE CHEMISTRY (2024):16. |
入库方式: OAI收割
来源:上海药物研究所
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