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Chemo- and Site-Selective Lysine Modification of Peptides and Proteins under Native Conditions Using the Water-Soluble Zolinium

文献类型：期刊论文

作者Sun, Haiguo4,5,6; Xi, Mengyu4,5,6; Jin, Qiang3; Zhu, Zhengdan4,5,6; Zhang, Yani3; Jia, Guihua3; Zhu, Guanghao3; Sun, Mengru3; Zhang, Hongwei3; Ren, Xuelian4,5,6
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-08-22
页码14
ISSN号0022-2623
DOI10.1021/acs.jmedchem.2c00937
通讯作者Li, Bo(boli@simm.ac.cn) ; Ge, Guangbo(geguangbo@dicp.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn)
英文摘要Site-selective lysine modification of peptides and proteins in aqueous solutions or in living cells is still a big challenge today. Here, we report a novel strategy to selectively quinolylate lysine residues of peptides and proteins under native conditions without any catalysts using our newly developed water-soluble zoliniums. The zoliniums could site-selectively quinolylate K350 of bovine serum albumin and inactivate SARS-CoV-2 3CL(pro )via covalently modifying two highly conserved lysine residues (K5 and K61). In living HepG2 cells, it was demonstrated that the simple zoliniums (5b and 5B) could quinolylate protein lysine residues mainly in the nucleus, cytosol, and cytoplasm, while the zolinium-fluorophore hybrid (8) showed specific lysosome-imaging ability. The specific chemoselectivity of the zoliniums for lysine was validated by a mixture of eight different amino acids, different peptides bearing potential reactive residues, and quantum chemistry calculations. This study offers a new way to design and develop lysine-targeted covalent ligands for specific application.
WOS关键词COVALENT INHIBITORS ; DISCOVERY ; CHEMISTRY ; RESIDUES ; STRATEGY ; SHIFTS
资助项目Natural Science Foundation of China[22077131] ; Natural Science Foundation of China[81922070] ; Natural Science Foundation of China[81973286] ; Natural Science Foundation of China[81872797] ; National Key Research and Development Program of China[2016YFA0502301] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Shanghai Talent Development Fund[2019093] ; Natural Science Foundation of Shanghai, China[19ZR1467800] ; State Key Laboratory of Natural and Biomimetic Drugs[K202108]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000848533600001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/302105]  
专题新药研究国家重点实验室
通讯作者Li, Bo; Ge, Guangbo; Zhu, Weiliang
作者单位1.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Haiguo,Xi, Mengyu,Jin, Qiang,et al. Chemo- and Site-Selective Lysine Modification of Peptides and Proteins under Native Conditions Using the Water-Soluble Zolinium[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022:14.
APA Sun, Haiguo.,Xi, Mengyu.,Jin, Qiang.,Zhu, Zhengdan.,Zhang, Yani.,...&Zhu, Weiliang.(2022).Chemo- and Site-Selective Lysine Modification of Peptides and Proteins under Native Conditions Using the Water-Soluble Zolinium.JOURNAL OF MEDICINAL CHEMISTRY,14.
MLA Sun, Haiguo,et al."Chemo- and Site-Selective Lysine Modification of Peptides and Proteins under Native Conditions Using the Water-Soluble Zolinium".JOURNAL OF MEDICINAL CHEMISTRY (2022):14.

入库方式： OAI收割

来源：上海药物研究所

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