title: Peptide deformylase inhibitors with retro-amide scaffold: synthesis and structure-activity relationships.
abstract: Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins. Thus inhibition of PDF activity is considered to be one of the most effective antibiotic strategies. Reported herein are the synthesis and structure-activity relationship studies of retro-amide inhibitors based on actinonin, a naturally occurring PDF inhibitor. Analysis of the structure-activity relationships led to the discovery of 7a, which exhibits potent enzyme inhibition and antibacterial activity against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
authors.affiliation: Promeditech Ltd., College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Choi
authors.forename: Sang Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Se Won
authors.initials: SW
authors.lastname: Suh
authors.forename: B Moon
authors.initials: BM
authors.lastname: Kim
authors.forename: Bong Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D000581:Amidohydrolases; C084507:peptide deformylase; C010531:actinonin