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Bioorg Med Chem Lett. 2013 Oct 15;23(20):5654-9. doi: 10.1016/j.bmcl.2013.08.026. Epub 2013 Aug 14.

Efforts toward broadening the spectrum of arylomycin antibiotic activity.

Author information

1
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract

New antibiotics are needed, and one source may be 'latent' antibiotics, natural products whose once broad-spectrum activity is currently limited by the evolution of resistance in nature. We have identified a potential class of latent antibiotics, the arylomycins, which are lipopeptides with a C-terminal macrocycle that target signal peptidase and whose spectrum is limited by a resistance-conferring mutation in many bacteria. Herein, we report the synthesis and evaluation of several arylomycin derivatives, and demonstrate that both C-terminal homologation with a glycyl aldehyde and addition of a positive charge to the macrocycle increase the activity and spectrum of the arylomycin scaffold.

KEYWORDS:

C-terminal electrophile; Latent antibiotic; Protein secretion; Signal peptidase

PMID:
24012184
PMCID:
PMC3981466
DOI:
10.1016/j.bmcl.2013.08.026
[Indexed for MEDLINE]
Free PMC Article
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