Issue 31, 2013

Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase

Abstract

Tropolone emerged from the screening of a chelator fragment library (CFL) as an inhibitor of the Zn2+-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 viable scaffold for identifying first-in-class LasB inhibitors.

Graphical abstract: Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase

Supplementary files

Article information

Article type
Communication
Submitted
13 Cʼhwe. 2013
Accepted
05 Meur. 2013
First published
06 Meur. 2013

Chem. Commun., 2013,49, 3197-3199

Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase

J. L. Fullagar, A. L. Garner, A. K. Struss, J. A. Day, D. P. Martin, J. Yu, X. Cai, K. D. Janda and S. M. Cohen, Chem. Commun., 2013, 49, 3197 DOI: 10.1039/C3CC41191E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements