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Efforts toward broadening the spectrum of arylomycin antibiotic activity.

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.

SUBMITTER: Liu J

PROVIDER: S-EPMC3981466 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Efforts toward broadening the spectrum of arylomycin antibiotic activity.

Liu Jian J Smith Peter A PA Steed Danielle Barrios DB Romesberg Floyd F

Bioorganic & medicinal chemistry letters 20130814 20

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 de ...[more]

PMID: 24012184

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