Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A
文献类型：期刊论文
| 作者 | Hou, Xiaochen1,2; Wang, Meining4; Wen, Yi3; Ni, Tengfeng2; Guan, Xiangna; Lan, Lefu2 ; Zhang, Naixia3; Zhang, Ao4; Yang, Cai-Guang2
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2018-06-01 |
| 卷号 | 28期号:10页码:1864-1869 |
| 关键词 | Staphylococcus aureus Anti-virulence Sortase A Covalent inhibitor Quinone skeleton |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2018.04.005 |
| 文献子类 | Article |
| 英文摘要 | Sortase A (SrtA) anchors surface proteins to the cell wall and aids biofilm formation during infection, which functions as a key virulence factor of important Gram-positive pathogens, such as Staphylococcus aureus. At present researchers need a way in which to validate whether or not SrtA is a druggable target alternative to the conventional antibiotic targets in the mechanism. In this study, we performed a high-throughput screening and identified a new class of potential inhibitors of S. aureus SrtA, which are derived from natural products and contain the quinone skeleton. Compound 283 functions as an irreversible inhibitor that covalently alkylates the active site Cysl84 of SrtA. NMR analysis confirms the direct interaction of the small-molecule inhibitor towards SrtA protein. The anchoring of protein A (SpA) to the cell wall and the biofilm formation are significantly attenuated when the . aureus Newman strain is cultured in the presence of inhibitor. Our study indicates that compound 283 could be a potential hit for the development of new anti-virulence agents against S. aureus infections by covalently targeting SrtA. (C) 2018 Elsevier Ltd. All rights reserved. |
| WOS关键词 | GRAM-POSITIVE BACTERIA ; CELL-WALL ; SURFACE-PROTEINS ; TRANSPEPTIDASE-SRTA ; VIRULENCE ; DISCOVERY ; RECOGNITION ; INFECTIONS ; BIOFILMS ; CYSTEINE |
| 资助项目 | National Natural Science Foundation of China[81661138004] ; National Natural Science Foundation of China[21725801] ; Program of Shanghai Academic Research Leader[17XD1404400] ; Program of Shanghai Academic Research Leader[16XD1404600] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000432729000034 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279737]  |
| 专题 | 分析化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 药理学第三研究室 |
| 通讯作者 | Zhang, Naixia; Zhang, Ao; Yang, Cai-Guang |
| 作者单位 | 1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China; 3.Fudan Univ, Sch Pharm, Minist Educ, 826 ZhangHeng Rd, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 ZuChongZhi Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Hou, Xiaochen,Wang, Meining,Wen, Yi,et al. Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2018,28(10):1864-1869. |
| APA | Hou, Xiaochen.,Wang, Meining.,Wen, Yi.,Ni, Tengfeng.,Guan, Xiangna.,...&Yang, Cai-Guang.(2018).Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,28(10),1864-1869. |
| MLA | Hou, Xiaochen,et al."Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 28.10(2018):1864-1869. |
入库方式： OAI收割
来源：上海药物研究所
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