Elfamycins: inhibitors of elongation factor-Tu

• Type of Material: Article
• Authors: Samantha M. Prezioso, Emory University; Nicole E. Brown, Emory University; Joanna Goldberg, Emory University
• Language: English
• Date: 2017-10-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 John Wiley & Sons Ltd
• Final Published Version (URL): http://dx.doi.org/10.1111/mmi.13750
• Title of Journal or Parent Work: Molecular Microbiology
• ISSN: 0950-382X
• Volume: 106
• Issue: 1
• Start Page: 22
• End Page: 34
• Grant/Funding Information: SMP was supported in part by a training grant from the National Institute of Allergy and Infectious Diseases of the NIH to Emory University (T32AI106699, Antimicrobial Resistance and Therapeutic Discovery Training Program).; Molecular graphics and analyses were performed with the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).
• Keywords: BIOSYNTHETIC GENE-CLUSTER; CLOSTRIDIUM-DIFFICILE; Life Sciences & Biomedicine; CENTER-DOT-GTP; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; Biochemistry & Molecular Biology; Science & Technology; GUANINE-NUCLEOTIDE EXCHANGE; ENACYLOXIN-IIA; Microbiology; GRAM-NEGATIVE BACTERIA; AMINOACYL-TRANSFER-RNA; FACTOR EF-TU
• Research Categories: Biology, Microbiology; Chemistry, Biochemistry; Biology, Molecular

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.