Site- and Stereoselective Glycomodification of Biomolecules through Carbohydrate-Promoted Pictet-Spengler Reaction
文献类型：期刊论文
| 作者 | Liu, Bo5,6; Zou, Xiangman3,4,5; Zhang, Yue3,4,5; Yang, Yang5,6; Xu, Hao2,5; Tang, Feng4,5; Yu, Huixin3,4,5; Xia, Fei4,5; Liu, Zhi5; Zhao, Jianwei1 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
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| 出版日期 | 2024-03-11 |
| 页码 | 11 |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202401394 |
| 通讯作者 | Huang, Wei(huangwei@simm.ac.cn) |
| 英文摘要 | Carbohydrates play pivotal roles in an array of essential biological processes and are consequently involved in many diseases. To meet the needs of glycobiology research, chemical enzymatic and non-enzymatic methods have been developed to generate glycoconjugates with well-defined structures. Herein, harnessing the unique properties of C6-oxidized glycans, we report a straightforward and robust strategy for site- and stereoselective glycomodification of biomolecules with N-terminal tryptophan residues by a carbohydrate-promoted Pictet-Spengler reaction, which is not adapted to typical aldehyde substrates under biocompatible conditions. This method reliably delivers highly homogeneous glycoconjugates with stable linkages and thus has great potential for functional modulation of peptides and proteins in glycobiology research. Moreover, this reaction can be performed at the glycosites of glycopeptides, glycoproteins and living-cell surfaces in a site-specific manner. Control experiments indicated that the protected alpha-O atom of aldehyde donors and free N-H bond of the tryptamine motif are crucial for this reaction. Mechanistic investigations demonstrated that the reaction exhibited a first-order dependence on both tryptophan and glycan, and deprotonation/rearomatization of the pentahydro-beta-carbolinium ion intermediate might be the rate-determining step. A glycomodification strategy targeting N-terminal tryptophan of biomolecules was developed using C6-oxidized glycans through a carbohydrate-promoted Pictet-Spengler reaction, providing homogeneous glycoconjugates with stable linkages. This method features high efficiency, mild conditions, robustness, biocompatibility, and applicability to a wide range of substrates, including glycans, peptides, proteins, and living-cell surfaces. image |
| WOS关键词 | SOLID-PHASE SYNTHESIS ; PROTEIN GLYCOSYLATION ; CHEMICAL-SYNTHESIS ; PEPTIDES ; LIGATION ; IGG ; GLYCOSYLTRANSFERASES ; MECHANISMS ; GENERATION ; STRATEGIES |
| 资助项目 | National Natural Science Foundation of China[82325045] ; National Natural Science Foundation of China[92153301] ; National Natural Science Foundation of China[82003574] ; Natural Science Foundation of China (NSFC)[19YF1457100] ; Natural Science Foundation of China (NSFC)[22YF1457400] ; Shanghai Sail Program[LG-QS-202206-03] ; Shanghai Municipal Science and Technology Major Project, Hangzhou innovation and entrepreneurship leading team project |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001181842900001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310112]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Huang, Wei |
| 作者单位 | 1.Shenzhen HUASUAN Technol Co Ltd, Shenzhen 518055, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Rd, Nanjing 210023, Peoples R China 3.Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China 4.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 6.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Bo,Zou, Xiangman,Zhang, Yue,et al. Site- and Stereoselective Glycomodification of Biomolecules through Carbohydrate-Promoted Pictet-Spengler Reaction[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2024:11. |
| APA | Liu, Bo.,Zou, Xiangman.,Zhang, Yue.,Yang, Yang.,Xu, Hao.,...&Huang, Wei.(2024).Site- and Stereoselective Glycomodification of Biomolecules through Carbohydrate-Promoted Pictet-Spengler Reaction.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,11. |
| MLA | Liu, Bo,et al."Site- and Stereoselective Glycomodification of Biomolecules through Carbohydrate-Promoted Pictet-Spengler Reaction".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2024):11. |
入库方式： OAI收割
来源：上海药物研究所
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