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dc.contributor.authorLu, Cenbin
dc.contributor.authorKirsch, Benjamin
dc.contributor.authorZimmer, Christina
dc.contributor.authorde Jong, Johannes C
dc.contributor.authorHenn, Claudia
dc.contributor.authorMaurer, Christine K
dc.contributor.authorMüsken, Mathias
dc.contributor.authorHäussler, Susanne
dc.contributor.authorSteinbach, Anke
dc.contributor.authorHartmann, Rolf W
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.
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
refterms.dateFOA2018-06-13T07:19:15Z
html.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.


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