Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa.

2.50
Hdl Handle:
http://hdl.handle.net/10033/237555
Title:
Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa.
Authors:
Lu, Cenbin; Kirsch, Benjamin; Zimmer, Christina; de Jong, Johannes C; Henn, Claudia; Maurer, Christine K; Müsken, Mathias; Häussler, Susanne; Steinbach, Anke; Hartmann, Rolf W
Abstract:
The pqs quorum sensing communication system of Pseudomonas aeruginosa controls virulence factor production and is involved in biofilm formation, therefore playing an important role for pathogenicity. In order to attenuate P. aeruginosa pathogenicity, we followed a ligand-based drug design approach and synthesized a series of compounds targeting PqsR, the receptor of the pqs system. In vitro evaluation using a reporter gene assay in Escherichia coli led to the discovery of the first competitive PqsR antagonists, which are highly potent (K(d,app) of compound 20: 7 nM). These antagonists are able to reduce the production of the virulence factor pyocyanin in P. aeruginosa. Our finding offers insights into the ligand-receptor interaction of PqsR and provides a promising starting point for further drug design.
Affiliation:
Helmholtz Institute for Pharmaceutical Research Saarland, Campus C2.3, 66123 Saarbrücken, Germany.
Citation:
Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa. 2012, 19 (3):381-90 Chem. Biol.
Journal:
Chemistry & biology
Issue Date:
23-Mar-2012
URI:
http://hdl.handle.net/10033/237555
DOI:
10.1016/j.chembiol.2012.01.015
PubMed ID:
22444593
Type:
Article
Language:
en
ISSN:
1879-1301
Appears in Collections:
Publications of the divsion Wirkstoffdesign und Optimierung (DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorLu, Cenbinen_GB
dc.contributor.authorKirsch, Benjaminen_GB
dc.contributor.authorZimmer, Christinaen_GB
dc.contributor.authorde Jong, Johannes Cen_GB
dc.contributor.authorHenn, Claudiaen_GB
dc.contributor.authorMaurer, Christine Ken_GB
dc.contributor.authorMüsken, Mathiasen_GB
dc.contributor.authorHäussler, Susanneen_GB
dc.contributor.authorSteinbach, Ankeen_GB
dc.contributor.authorHartmann, Rolf Wen_GB
dc.date.accessioned2012-08-07T13:35:08Z-
dc.date.available2012-08-07T13:35:08Z-
dc.date.issued2012-03-23-
dc.identifier.citationDiscovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa. 2012, 19 (3):381-90 Chem. Biol.en_GB
dc.identifier.issn1879-1301-
dc.identifier.pmid22444593-
dc.identifier.doi10.1016/j.chembiol.2012.01.015-
dc.identifier.urihttp://hdl.handle.net/10033/237555-
dc.description.abstractThe pqs quorum sensing communication system of Pseudomonas aeruginosa controls virulence factor production and is involved in biofilm formation, therefore playing an important role for pathogenicity. In order to attenuate P. aeruginosa pathogenicity, we followed a ligand-based drug design approach and synthesized a series of compounds targeting PqsR, the receptor of the pqs system. In vitro evaluation using a reporter gene assay in Escherichia coli led to the discovery of the first competitive PqsR antagonists, which are highly potent (K(d,app) of compound 20: 7 nM). These antagonists are able to reduce the production of the virulence factor pyocyanin in P. aeruginosa. Our finding offers insights into the ligand-receptor interaction of PqsR and provides a promising starting point for further drug design.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Chemistry & biologyen_GB
dc.subject.mesh4-Quinolonesen_GB
dc.subject.meshBacterial Proteinsen_GB
dc.subject.meshDrug Designen_GB
dc.subject.meshGenes, Reporteren_GB
dc.subject.meshKineticsen_GB
dc.subject.meshPseudomonas aeruginosaen_GB
dc.subject.meshPyocyanineen_GB
dc.subject.meshQuorum Sensingen_GB
dc.titleDiscovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research Saarland, Campus C2.3, 66123 Saarbrücken, Germany.en_GB
dc.identifier.journalChemistry & biologyen_GB

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