Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor

Joseph N. Capilato; Shane V. Philippi; Thomas Reardon; Ashleigh McConnell; Dylan C. Oliver; Amy Warren; Jill S. Adams; Chun Wu; Lark J. Perez

doi:10.1016/j.bmc.2016.10.021

Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor

Joseph N. Capilato, Shane V. Philippi, Thomas Reardon, Ashleigh McConnell, Dylan C. Oliver, Amy Warren, Jill S. Adams, Chun Wu, Lark J. Perez

Chemistry

Rowan University

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	American English
Pages (from-to)	153-165
Number of pages	13
Journal	Bioorganic and Medicinal Chemistry
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.bmc.2016.10.021
State	Published - 2017

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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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.",

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AU - Capilato, Joseph N.

AU - Philippi, Shane V.

AU - Reardon, Thomas

AU - McConnell, Ashleigh

AU - Oliver, Dylan C.

AU - Warren, Amy

AU - Adams, Jill S.

AU - Wu, Chun

AU - Perez, Lark J.

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AB - 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.

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Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor

Abstract

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