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精灵霉素:延伸因子-Tu的抑制剂。

Elfamycins: inhibitors of elongation factor-Tu.

作者信息

Prezioso Samantha M, Brown Nicole E, Goldberg Joanna B

机构信息

Microbiology and Molecular Genetics Program, Graduate Division of Biological and Biomedical Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.

Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.

出版信息

Mol Microbiol. 2017 Oct;106(1):22-34. doi: 10.1111/mmi.13750. Epub 2017 Aug 9.

Abstract

Elfamycins are a relatively understudied group of antibiotics that target the essential process of translation through impairment of EF-Tu function. For the most part, the utility of these compounds has been as laboratory tools for the study of EF-Tu and the ribosome, as their poor pharmacokinetic profile and solubility has prevented implementation as therapeutic agents. However, due to the slowing of the antibiotic pipeline and the rapid emergence of resistance to approved antibiotics, this group is being reconsidered. Some researchers are using screens for novel naturally produced variants, while others are making directed, systematic chemical improvements on publically disclosed compounds. As an example of the latter approach, a GE2270 A derivative, LFF571, has completed phase 2 clinical trials, thus demonstrating the potential for elfamycins to become more prominent antibiotics in the future.

摘要

厄尔法霉素是一类研究相对较少的抗生素,它们通过损害EF-Tu的功能来靶向翻译这一基本过程。在很大程度上,这些化合物的用途一直是作为研究EF-Tu和核糖体的实验室工具,因为它们较差的药代动力学特性和溶解性阻碍了其作为治疗药物的应用。然而,由于抗生素研发进程放缓以及对已批准抗生素耐药性的迅速出现,这一类抗生素正被重新审视。一些研究人员正在筛选新型天然产生的变体,而另一些人则对公开披露的化合物进行定向、系统的化学改进。作为后一种方法的一个例子,一种GE2270 A衍生物LFF571已经完成了2期临床试验,从而证明了厄尔法霉素在未来成为更重要抗生素的潜力。

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