Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor. Issue 1 (1st January 2017)

• Record Type: Journal Article
• Authors: Capilato, Joseph N.; Philippi, Shane V.; Reardon, Thomas; McConnell, Ashleigh; Oliver, Dylan C.; Warren, Amy; Adams, Jill S.; Wu, Chun; Perez, Lark J.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 1(2017)
• Page Start: 153
• Page End: 165
• Publication Date: 2017-01-01
• Subjects: Anti-virulence -- Pseudomonas aeruginosa -- Structure–activity relationship -- Computational modeling -- Quorum sensing; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.10.021
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Bacterial chemical communication, through a process called quorum sensing (QS), plays a central role in infection in numerous bacterial pathogens. Quorum sensing in Pseudomonas aeruginosa employs a series of small molecule receptors including the master QS regulator, LasR. In this study we investigate a non-natural triaryl series of LasR ligands using a combination of structure activity relationship studies and computational modeling. These studies have enabled the identification of key structural requirements for ligand binding and have revealed a new strategy for inducing the therapeutically relevant antagonism of LasR.