Synthesis and biological evaluation of penem inhibitors of bacterial signal peptidase.
We report the first synthesis of a 5S penem, known to bind bacterial type I signal peptidase, from the commercially available and inexpensive 6-aminopenicillanic acid. We report the first in vivo activity of the compound and use structure-activity relationship studies to begin to define the determinants of signal peptidase binding and also to begin to optimize the penem as an antibiotic.
Harris
David A
DA
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Powers
Michael E
ME
Romesberg
Floyd E
FE
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D008565:Membrane Proteins; D015842:Serine Proteinase Inhibitors; D010397:Penicillanic Acid; D012697:Serine Endopeptidases; C026515:type I signal peptidase; C004408:aminopenicillanic acid