Chemical Space Profiling of SARS-CoV-2 PLpro Using DNA-Encoded Focused Libraries
文献类型：期刊论文
| 作者 | Wang, Xudong2,4; Zhu, Ying3; Zhao, Qingyi3; Lu, Weiwei4; Xu, Yechun3,4 ; Hu, Hangchen1,4; Lu, Xiaojie2,3,4
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| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2024-03-14 |
| 页码 | 10 |
| ISSN号 | 1948-5875 |
| 关键词 | DNA-Encoded Focused Libraries (DEFLs) SARS-CoV-2 Papain-like Protease Library Design ProteinInhibitors |
| DOI | 10.1021/acsmedchemlett.4c00069 |
| 通讯作者 | Hu, Hangchen(201728012342070@simm.ac.cn) ; Lu, Xiaojie(xjlu@simm.ac.cn) |
| 英文摘要 | DNA-encoded library (DEL) technology is gaining attention for its rapid construction and deconvolution capabilities. Our study explored a novel strategy using rational DELs tailored for the SARS-CoV-2 papain-like protease, which revealed new fragments. Structural changes post-DEL screening mimic traditional medicinal chemistry lead optimization. We unveiled unique aromatic structures offering an alternative optimization path. Notably, we identified superior binding fragments targeting the BL2 groove. Derivative 16 emerged as the most promising by exhibiting IC50 values of 0.25 mu M. Derivative 6, which features an aromatic fragment capped with a naphthalene moiety, showed IC50 values of 2.91 mu M. Molecular modeling revealed hydrogen bond interactions with Lys157 residue and potential covalent interactions with nearby amino acid residues. This research underscored DEL's potential for fragment-based drug discovery against SARS-CoV-2 protease. |
| WOS关键词 | INHIBITORS ; DISCOVERY ; PROTEASE ; POTENT |
| 资助项目 | National Natural Science Foundation of China[NSFC-91953203] ; National Natural Science Foundation of China[NSFC- 92253305] ; National Natural Science Foundation of China[32301050] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:001185413000001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310178]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Hangchen; Lu, Xiaojie |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Xudong,Zhu, Ying,Zhao, Qingyi,et al. Chemical Space Profiling of SARS-CoV-2 PLpro Using DNA-Encoded Focused Libraries[J]. ACS MEDICINAL CHEMISTRY LETTERS,2024:10. |
| APA | Wang, Xudong.,Zhu, Ying.,Zhao, Qingyi.,Lu, Weiwei.,Xu, Yechun.,...&Lu, Xiaojie.(2024).Chemical Space Profiling of SARS-CoV-2 PLpro Using DNA-Encoded Focused Libraries.ACS MEDICINAL CHEMISTRY LETTERS,10. |
| MLA | Wang, Xudong,et al."Chemical Space Profiling of SARS-CoV-2 PLpro Using DNA-Encoded Focused Libraries".ACS MEDICINAL CHEMISTRY LETTERS (2024):10. |
入库方式： OAI收割
来源：上海药物研究所
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