Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase.
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ABSTRACT:
SUBMITTER: Fullagar JL
PROVIDER: S-EPMC3618488 | biostudies-literature | 2013 Apr
REPOSITORIES: biostudies-literature
Publications
Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase.
Fullagar Jessica L JL Garner Amanda L AL Struss Anjali K AK Day Joshua A JA Martin David P DP Yu Jing J Cai Xiaoqing X Janda Kim D KD Cohen Seth M SM
Chemical communications (Cambridge, England) 20130312 31
Tropolone emerged from the screening of a chelator fragment library (CFL) as an inhibitor of the Zn(2+)-dependent virulence factor, Pseudomonas aeruginosa elastase (LasB). Based on this initial hit, a series of substituted tropolone-based LasB inhibitors was prepared, and a compound displaying potent activity in vitro and in a bacterial swarming assay was identified. Importantly, this inhibitor was found to be specific for LasB over other metalloenzymes, validating the usage of tropolone as a vi ...[more]
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