GSTDTAP  > 资源环境科学
DOI10.1038/ncomms14365
Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E
Itoh, Hiroaki1; Tokumoto, Kotaro1; Kaji, Takuya1; Paudel, Atmika2; Panthee, Suresh2; Hamamoto, Hiroshi2; Sekimizu, Kazuhisa2; Inoue, Masayuki1
2019-07-05
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2019
卷号10
文章类型Article
语种英语
国家Japan
英文摘要

Lysocin E, a 37-membered natural depsipeptide, induces rapid bacteriolysis in methicillin-resistant Staphylococcus aureus via a unique menaquinone-dependent mechanism, presenting a promising therapeutic lead. Despite the great medical importance, exploring the potential utility of its derivatives as new platform structures for antibiotic development has remained a significant challenge. Here, we report a high-throughput strategy that enabled the preparation of thousands of analogues of lysocin E and large-scale structure-activity relationship analyses. We integrate 26-step total synthesis of 2401 cyclic peptides, tandem mass spectrometry-sequencing, and two microscale activity assays to identify 23 candidate compounds. Re-synthesis of these candidates shows that 11 of them (A1-A11) exhibit antimicrobial activity superior or comparable to that of lysocin E, and that lysocin E and A1-A11 share L-Leu-6 and L-IIe-11. Therefore, the present strategy allows us to efficiently decipher biologically crucial residues and identify potentially useful agents for the treatment of infectious diseases.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000474241100001
WOS关键词SOLID-PHASE SYNTHESIS ; CHEMICAL-SYNTHESIS ; NATURAL-PRODUCTS ; COMBINATORIAL LIBRARIES ; PEPTIDE ; MENAQUINONE ; CHEMISTRY ; BIOLOGY ; MICROWAVE
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
URL查看原文
引用统计
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/203206
专题资源环境科学
作者单位1.Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan;
2.Teikyo Univ, Inst Med Mycol, 359 Otsuka, Hachioji, Tokyo 1920395, Japan
推荐引用方式
GB/T 7714
Itoh, Hiroaki,Tokumoto, Kotaro,Kaji, Takuya,et al. Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E[J]. NATURE COMMUNICATIONS,2019,10.
APA Itoh, Hiroaki.,Tokumoto, Kotaro.,Kaji, Takuya.,Paudel, Atmika.,Panthee, Suresh.,...&Inoue, Masayuki.(2019).Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E.NATURE COMMUNICATIONS,10.
MLA Itoh, Hiroaki,et al."Development of a high-throughput strategy for discovery of potent analogues of antibiotic lysocin E".NATURE COMMUNICATIONS 10(2019).
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Itoh, Hiroaki]的文章
[Tokumoto, Kotaro]的文章
[Kaji, Takuya]的文章
百度学术
百度学术中相似的文章
[Itoh, Hiroaki]的文章
[Tokumoto, Kotaro]的文章
[Kaji, Takuya]的文章
必应学术
必应学术中相似的文章
[Itoh, Hiroaki]的文章
[Tokumoto, Kotaro]的文章
[Kaji, Takuya]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

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。