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DOI | 10.1038/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
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ISSN | 2041-1723 |
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). |
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