Peptide deformylase inhibitors with retro-amide scaffold: synthesis and structure-activity relationships
Seung Kyu Lee1, Kwang Hyun Choi, Sang Jae Lee
1Promeditech Ltd., College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
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.
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