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.
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
David A
DA
Harris
Michael E
ME
Powers
Floyd E
FE
Romesberg
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