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DOI | 10.1016/j.landurbplan.2016.07.002 |
Predictive compound accumulation rules yield a broad - spectrum antibiotic | |
Richter, Michelle F.1,2; Drown, Bryon S.1,2; Riley, Andrew P.1,2; Garcia, Alfredo1,2; Shirai, Tomohiro1,2; Svec, Riley L.1,2; Hergenrother, Paul J.1,2 | |
2017-05-18 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 545期号:7654页码:299-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000401466500053 |
WOS关键词 | DRUG-LIKE MOLECULES ; ADENOSINE-DIPHOSPHATE (HYDROXYMETHYL)PYRROLIDINEDIOL ; ESCHERICHIA-COLI ; OUTER-MEMBRANE ; OMPF PORIN ; ANTIBACTERIAL DISCOVERY ; RING-DISTORTION ; POLY(ADP-RIBOSE) GLYCOHYDROLASE ; DYNAMICS SIMULATION ; DIVERSE COMPOUNDS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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/25283 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Illinois, Dept Chem, Urbana, IL 61801 USA; 2.Inst Genom Biol, Urbana, IL 61801 USA |
推荐引用方式 GB/T 7714 | Richter, Michelle F.,Drown, Bryon S.,Riley, Andrew P.,et al. Predictive compound accumulation rules yield a broad - spectrum antibiotic[J]. NATURE,2017,545(7654):299-+. |
APA | Richter, Michelle F..,Drown, Bryon S..,Riley, Andrew P..,Garcia, Alfredo.,Shirai, Tomohiro.,...&Hergenrother, Paul J..(2017).Predictive compound accumulation rules yield a broad - spectrum antibiotic.NATURE,545(7654),299-+. |
MLA | Richter, Michelle F.,et al."Predictive compound accumulation rules yield a broad - spectrum antibiotic".NATURE 545.7654(2017):299-+. |
条目包含的文件 | 条目无相关文件。 |
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