Discovery of Thioether-Cyclized Macrocyclic Covalent Inhibitors by mRNA Display
文献类型：期刊论文
| 作者 | Lan, Tong6; Peng, Cheng6; Yao, Xiyuan6; Chan, Rachel Shu Ting6; Wei, Tongyao6; Rupanya, Anuchit6; Radakovic, Aleksandar6; Wang, Sijie5; Chen, Shiyu4,5; Lovell, Scott3,5 |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
 |
| 出版日期 | 2024-08-13 |
| 卷号 | 146期号:34页码:24053-24060 |
| ISSN号 | 0002-7863 |
| DOI | 10.1021/jacs.4c07851 |
| 通讯作者 | Dickinson, Bryan C.(Dickinson@uchicago.edu) |
| 英文摘要 | Macrocyclic peptides are promising scaffolds for the covalent ligand discovery. However, platforms enabling the direct identification of covalent macrocyclic ligands in a high-throughput manner are limited. In this study, we present an mRNA display platform allowing selection of covalent macrocyclic inhibitors using 1,3-dibromoacetone-vinyl sulfone (DBA-VS). Testcase selections on TEV protease resulted in potent covalent inhibitors with diverse cyclic structures, among which cTEV6-2, a macrocyclic peptide with a unique C-terminal cyclization, emerged as the most potent covalent inhibitor of TEV protease described to-date. This study outlines the workflow for integrating chemical functionalization & horbar;installation of a covalent warhead & horbar;with mRNA display and showcases its application in targeted covalent ligand discovery. |
| WOS关键词 | IN-VITRO SELECTION ; PEPTIDES ; FUSIONS |
| 资助项目 | National Institute of General Medical Sciences of the National Institutes of Health NIH[R35 GM119840] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001291129900001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312800]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Dickinson, Bryan C. |
| 作者单位 | 1.Chan Zuckerberg Biohub, Chicago, IL 60642 USA 2.Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA 3.Univ Bath, Dept Biol & Biochem, Claverton Down BA2 7AY, Bath, England 4.Chinese Acad Sci, Shanghai Inst Mat Med, Biotech Drug Res Ctr, Shanghai 201203, Peoples R China 5.Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA 6.Univ Chicago, Dept Chem, Chicago, IL 60637 USA |
| 推荐引用方式 GB/T 7714 | Lan, Tong,Peng, Cheng,Yao, Xiyuan,et al. Discovery of Thioether-Cyclized Macrocyclic Covalent Inhibitors by mRNA Display[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2024,146(34):24053-24060. |
| APA | Lan, Tong.,Peng, Cheng.,Yao, Xiyuan.,Chan, Rachel Shu Ting.,Wei, Tongyao.,...&Dickinson, Bryan C..(2024).Discovery of Thioether-Cyclized Macrocyclic Covalent Inhibitors by mRNA Display.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,146(34),24053-24060. |
| MLA | Lan, Tong,et al."Discovery of Thioether-Cyclized Macrocyclic Covalent Inhibitors by mRNA Display".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 146.34(2024):24053-24060. |
入库方式： OAI收割
来源：上海药物研究所
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