Single Modification at the N-Terminus of Norvancomycin to Combat Drug-Resistant Gram-Positive Bacteria
文献类型：期刊论文
| 作者 | Guan, Dongliang5,6; Chen, Feifei3; Shi, Wei1,6; Lan, Lefu2,3,4 ; Huang, Wei1,2,4,6
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| 刊名 | CHEMMEDCHEM
 |
| 出版日期 | 2023-05-02 |
| 卷号 | 18期号:9 |
| 关键词 | norvancomycin glycopeptide antibiotics single modification sulfonium bacterial resistance |
| DOI | 10.1002/cmdc.202200708 |
| 文献子类 | Article |
| 英文摘要 | In the arsenal of glycopeptide antibiotics, norvancomycin, which differs from vancomycin by a single methyl group, has received much less attention. Facing the risks of serious antibiotic resistance and even the collapse of last-line defenses, we designed and synthesized 40 novel norvancomycin derivatives to combat the threat. 32 compounds are single N-terminally modified derivatives generated through simple and efficient methods. Diversity at the N-terminus was greatly enriched, mainly by lipophilic attachment and strategies for the introduction of lipo-sulfonium moieties for extensive structure-activity relationship analysis. The first incorporation of a sulfonium moiety into the norvancomycin structure gave rise to compounds that exhibited 4- to 2048-fold higher activity against vancomycin-resistant bacteria VISA and VRE. This N-terminal modification for norvancomycin provides an alternatively useful and promising strategy to restore the antibacterial activity of glycopeptide antibiotics against resistant bacteria, highlighting the same importance of the N-terminal site as well as the vancosamine position, which is worth further study and development. |
| WOS关键词 | CELL-WALL BIOSYNTHESIS ; VANCOMYCIN DIMERS ; GLYCOPEPTIDE ANTIBIOTICS ; PERIPHERAL MODIFICATIONS ; ANTIBACTERIAL ACTIVITY ; STAPHYLOCOCCUS-AUREUS ; POTENT ACTIVITY ; DEMETHYLVANCOMYCIN ; ANALOGS ; TD-1792 |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000948766300001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309672]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Guan, Dongliang; Lan, Lefu; Huang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Biotherapeut Discovery Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China; 5.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yanta 264117, Shandong, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Guan, Dongliang,Chen, Feifei,Shi, Wei,et al. Single Modification at the N-Terminus of Norvancomycin to Combat Drug-Resistant Gram-Positive Bacteria[J]. CHEMMEDCHEM,2023,18(9). |
| APA | Guan, Dongliang,Chen, Feifei,Shi, Wei,Lan, Lefu,&Huang, Wei.(2023).Single Modification at the N-Terminus of Norvancomycin to Combat Drug-Resistant Gram-Positive Bacteria.CHEMMEDCHEM,18(9). |
| MLA | Guan, Dongliang,et al."Single Modification at the N-Terminus of Norvancomycin to Combat Drug-Resistant Gram-Positive Bacteria".CHEMMEDCHEM 18.9(2023). |
入库方式： OAI收割
来源：上海药物研究所
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