title: 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Smith
authors.forename: Danielle Barrios
authors.initials: DB
authors.lastname: Steed
authors.forename: Floyd
authors.initials: F
authors.lastname: Romesberg
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic
keywords: C-terminal electrophile; Latent antibiotic; Protein secretion; Signal peptidase