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

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• 作者：Joseph N. Capilato ; Shane V. Philippi ; Thomas Reardon ; Ashleigh McConnell ; Dylan C. Oliver ; Amy Warren ; Jill S. Adams ; Chun Wu ; Lark J. Perez
• 关键词：Anti-virulence ; Pseudomonas aeruginosa ; Structure&ndash ; activity relationship ; Computational modeling ; Quorum sensing
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：153-165
• 全文大小：1732 K
• 卷排序：25

文摘

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.