Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors.
Macrocyclic peptidyl hydroxamates were designed, synthesized, and evaluated as peptide deformylase (PDF) inhibitors. The most potent compound exhibited tight, slow-binding inhibition of Escherichia coli PDF (K(I)(*)=4.4 nM) and had potent antibacterial activity against Gram-positive bacterium Bacillus subtilis (MIC=2-4 microg/mL).
Shen
Gang
G
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA.
Zhu
Jinge
J
Simpson
Anthony M
AM
Pei
Dehua
D
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects*; D001667:Binding, Competitive / Q000187:drug effects; D002208:Caproates / Q000737:chemistry; D015195:Drug Design; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002208:Caproates; D006877:Hydroxamic Acids; D010456:Peptides, Cyclic; D000581:Amidohydrolases; C084507:peptide deformylase