中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors

文献类型：期刊论文

作者Yue, Chuan2,3; Yuan, Ziqi3,4; Xu, Guobin1,3,5,6; Guan, Xiang-Na3,4; Wei, Bingyan3,4,7; Yao, Hequan1,6; Yang, Cai-Guang2,3,4,7; Zhang, Tao3
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2024-01-03
卷号67期号:2页码:1127-1146
ISSN号0022-2623
DOI10.1021/acs.jmedchem.3c01615
通讯作者Yang, Cai-Guang(yangcg@simm.ac.cn) ; Zhang, Tao(zhangtao@simm.ac.cn)
英文摘要Sortase A (SrtA) is a membrane-associated cysteine transpeptidase required for bacterial virulence regulation and anchors surface proteins to cell wall, thereby assisting biofilm formation. SrtA is targeted in antivirulence treatments against Gram-positive bacterial infections. However, the development of potent small-molecule SrtA inhibitors is constrained owing to the limited understanding of the mode of action of inhibitors in the SrtA binding pocket. Herein, we designed and synthesized a novel class of covalent SrtA inhibitors based on the binding mode detailed in the X-ray crystal structure of the ML346/Streptococcus pyogenes SrtA complex. ML346 analog Y40 exhibited 2-fold increased inhibitory activity on Staphylococcus aureus SrtA and showed superior inhibitory effects on biofilm formation in vitro. Y40 protected Galleria mellonella larvae fromS. aureusinfections in vivo while minimally attenuating staphylococcal growth in vitro. Our study indicates that the covalent SrtA inhibitor Y40 is an antivirulence agent that is effective againstS. aureusinfections.
WOS关键词SURFACE-PROTEINS ; INDUCED PNEUMONIA ; PROTECTS MICE ; VIRULENCE ; TARGET ; STRATEGIES ; PATHOGENESIS ; ENZYME ; SERIES ; MRSA
资助项目Youth Innovation Promotion Association of the Chinese Academy of Sciences[81861138046] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[22107109] ; National Natural Science Foundation of China[2023297] ; Youth Innovation Promotion Association of CAS
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:001151601900001
源URL[http://119.78.100.183/handle/2S10ELR8/308927]  
专题新药研究国家重点实验室
通讯作者Yang, Cai-Guang; Zhang, Tao
作者单位1.China Pharmaceut Univ, Sch Pharm, Dept Med Chem, Nanjing 210009, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.China Pharmaceut Univ, Sch Pharm, State Key Lab Nat Med, Nanjing 210009, Peoples R China
7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Yue, Chuan,Yuan, Ziqi,Xu, Guobin,et al. Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024,67(2):1127-1146.
APA Yue, Chuan.,Yuan, Ziqi.,Xu, Guobin.,Guan, Xiang-Na.,Wei, Bingyan.,...&Zhang, Tao.(2024).Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,67(2),1127-1146.
MLA Yue, Chuan,et al."Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 67.2(2024):1127-1146.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。