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Bioinspired Methionine-Selective Desulfurization Editing of Peptides via the Photocatalysis Strategy

文献类型：期刊论文

作者Zhang, Yue2,3,5; Yu, Huixin3,5; Tang, Feng3; Zhang, Feng-Hua2; Zhang, Meihui5; Dong, Jinhua5; Zhao, Jianwei1; Huang, Wei2,3,4; Liu, Bo2,3
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2025-05-05
卷号147期号:19页码:16379-16389
ISSN号0002-7863
DOI10.1021/jacs.5c02226
英文摘要S-Adenosylmethionine (SAM) frequently functions as a cofactor or precursor for enzymes, initiating an array of radical reactions in biological systems. In contrast with the conventional 5 '-deoxyadenosyl (dAdo) radical pathway, which proceeds via homolytic cleavage of the S-C(5 ') bond of SAM, the Dph2 enzyme provides an alternative 3-amino-3-carboxypropyl (ACP) radical pathway through breaking the S-C(gamma) bond. Inspired by this distinctive bond cleavage mode, we have developed a chemically induced pathway to generate an ACP-type radical intermediate on methionine-based sulfonium. This strategy presents a novel desulfurization conjugation mode for methionine modification, diverging from previous approaches that conjugate onto the sulfur atom or the adjacent methyl group of methionine. The versatility of this strategy is demonstrated by the efficient functionalization of various peptides and peptide macrocyclizations. Density Functional Theory (DFT) calculations provide further insights into the mechanism of this desulfurization reaction, explaining the exceptional selectivity of homolytic cleavage of the S-C(gamma) bond of methionine-based sulfonium. The successful implementation of this novel desulfurization strategy represents a substantial advancement in the understanding of sulfonium-based intramolecular radical substitution reactions and provides new opportunities for the functionalization of biomolecules, thereby fostering progress in interdisciplinary research.
WOS关键词S-ADENOSYLMETHIONINE ; HOMOLYTIC SUBSTITUTION ; RHODIUM CARBENOIDS ; NATIVE PROTEINS ; FUNCTIONALIZATION ; BIOCONJUGATION ; BIOSYNTHESIS ; RESIDUES ; CLEAVAGE ; ALKYLATION
资助项目National Natural Science Foundation of China[82325045] ; National Natural Science Foundation of China[22422705] ; National Natural Science Foundation of China[92478204] ; National Natural Science Foundation of China[22337003] ; National Natural Science Foundation of China[22277126] ; Natural Science Foundation of China (NSFC)
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001481569000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/317617]  
专题新药研究国家重点实验室
通讯作者Tang, Feng; Huang, Wei; Liu, Bo
作者单位1.Shenzhen HUASUAN Technol Co Ltd, Shenzhen 518055, Peoples R China
2.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Yue,Yu, Huixin,Tang, Feng,et al. Bioinspired Methionine-Selective Desulfurization Editing of Peptides via the Photocatalysis Strategy[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2025,147(19):16379-16389.
APA Zhang, Yue.,Yu, Huixin.,Tang, Feng.,Zhang, Feng-Hua.,Zhang, Meihui.,...&Liu, Bo.(2025).Bioinspired Methionine-Selective Desulfurization Editing of Peptides via the Photocatalysis Strategy.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,147(19),16379-16389.
MLA Zhang, Yue,et al."Bioinspired Methionine-Selective Desulfurization Editing of Peptides via the Photocatalysis Strategy".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147.19(2025):16379-16389.

入库方式： OAI收割

来源：上海药物研究所

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