Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor.
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.
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Joseph N
JN
Capilato
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Shane V
SV
Philippi
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Thomas
T
Reardon
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Ashleigh
A
McConnell
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Dylan C
DC
Oliver
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Amy
A
Warren
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Jill S
JS
Adams
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Chun
C
Wu
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Lark J
LJ
Perez
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D053038:Quorum Sensing / Q000187:drug effects*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D008024:Ligands; D015534:Trans-Activators
Anti-virulence; Computational modeling; Pseudomonas aeruginosa; Quorum sensing; Structure–activity relationship