Natural product derivatives with bactericidal activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis.
We have shown that the intentional engineering of a natural product biosynthesis pathway is a useful way to generate stereochemically complex scaffolds for use in the generation of combinatorial libraries that capture the structural features of both natural products and synthetic compounds. Analysis of a prototype library based upon nonactic acid lead to the discovery of triazole-containing nonactic acid analogs, a new structural class of antibiotic that exhibits bactericidal activity against drug resistant, Gram-positive pathogens including Staphylococcus aureus and Enterococcus faecalis.
Phillips
Joshua B
JB
Department of Chemistry, University of Montana, Missoula, MT 59812, USA.
Smith
Adrienne E
AE
Kusche
Brian R
BR
Bessette
Bradley A
BA
Swain
P Whitney
PW
Bergmeier
Stephen C
SC
McMills
Mark C
MC
Wright
Dennis L
DL
Priestley
Nigel D
ND
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001688:Biological Products; D018942:Macrolides; D014230:Triazoles; D014640:Vancomycin; C050476:nonactin
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