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
A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria

文献类型：期刊论文

作者Guan, Dongliang1,3,6; Li, Jian1,2,6; Chen, Feifei1,2,6; Li, Jiaqi4,5,6; Bian, Xiaolei3,6; Yu, Yue4,5,6; Feng, Xinxin4,5,6; Lan, Lefu2,6; Huang, Wei1,2,6
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2023-11-05
卷号259页码:14
ISSN号0223-5234
关键词Lipopeptide Daptomycin derivatives Multidrug-resistant bacteria Kynurenine Hexakynomycin
DOI10.1016/j.ejmech.2023.115638
通讯作者Guan, Dongliang(dlguan@baridd.ac.cn) ; Feng, Xinxin(xinxin_feng@hnu.edu.cn) ; Lan, Lefu(llan@ucas.ac.cn) ; Huang, Wei(huangwei@simm.ac.cn)
英文摘要Wide-spread use of daptomycin unavoidably resulted in the emergence of daptomycin-resistant pathogens. In the hunt for more active daptomycin derivatives through medicinal chemistry studies, we established a concise semisynthetic approach to modify the L-Kyn13 on daptomycin specifically and effectively. Here, 19 novel de-rivatives with certain diversity were designed and synthesized to perform a comprehensive SAR study on this underestimated position. The optimal compound, termed "hexakynomycin", as the new generation of daptomycin-based antibiotic candidate exhibited 4->125-fold higher activity against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE), including daptomycin-resistant strains, compared with that of daptomycin. Greater membrane binding capacity rendered hexakynomycin better activity and special antibiotic property. Hexakynomycin also demonstrated a better pharmacokinetic profile, good safety features and good pharmacodynamics properties. This work provided an effective modification strategy aiming at daptomycin which provided significant insights and showed great promise for the next generation of daptomycin derivatives.
WOS关键词BIOLOGICAL-ACTIVITY ; LIPOPEPTIDE ; ANALOGS ; A21978C
资助项目National Natural Science Foundation of China (NSFC)[21877116] ; National Natural Science Foundation of China (NSFC)[92153301] ; National Natural Science Foundation of China (NSFC)[32270184] ; National Natural Science Foundation of China (NSFC)[22177031] ; Hangzhou innovation and entrepreneurship leading team project[TD2020005]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号WOS:001047784900001
源URL[http://119.78.100.183/handle/2S10ELR8/307034]  
专题新药研究国家重点实验室
通讯作者Guan, Dongliang; Feng, Xinxin; Lan, Lefu; Huang, Wei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Biotherapeut Discovery Res, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
2.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
4.Hunan Univ, Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chemo Biosensing & Chemometr, Changsha 201203, Shanghai, Peoples R China
5.Hunan Univ, Chinese Acad Sci, Shanghai Inst Mat Med, Sch Chem & Chem Engn, Changsha 201203, Shanghai, Peoples R China
6.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Guan, Dongliang,Li, Jian,Chen, Feifei,et al. A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,259:14.
APA Guan, Dongliang.,Li, Jian.,Chen, Feifei.,Li, Jiaqi.,Bian, Xiaolei.,...&Huang, Wei.(2023).A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,259,14.
MLA Guan, Dongliang,et al."A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 259(2023):14.

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。