Design and Synthesis of a Biotinylated Chemical Probe for Detecting the Molecular Targets of an Inhibitor of the Production of the Pseudomonas aeruginosa Virulence Factor PyocyaninReport as inadecuate




Design and Synthesis of a Biotinylated Chemical Probe for Detecting the Molecular Targets of an Inhibitor of the Production of the Pseudomonas aeruginosa Virulence Factor Pyocyanin - Download this document for free, or read online. Document in PDF available to download.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK





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Abstract Pseudomonas aeruginosa is a human pathogen associated with a variety of life-threatening nosocomial infections. This organism produces a range of virulence factors which actively cause damage to host tissues. One such virulence factor is pyocyanin, known to play a crucial role in the pathogenesis of P. aeruginosa infections. Previous studies had identified a novel compound capable of strongly inhibiting the production of pyocyanin. It was postulated that this inhibition results from modulation of an intercellular communication system termed quorum sensing, via direct binding of the compound with the LasR protein receptor. This raised the possibility that the compound could be an antagonist of quorum sensing in P. aeruginosa, which could have important implications as this intercellular signaling mechanism is known to regulate many additional facets of P. aeruginosa pathogenicity. However, there was no direct evidence for the binding of the active compound to LasR or any other targets. Herein we describe the design and synthesis of a biotin-tagged version of the active compound. This could potentially be used as an affinity-based chemical probe to ascertain, in a direct fashion, the active compound’s macromolecular biological targets, and thus better delineate the mechanism by which it reduces the level of pyocyanin production. View Full-Text

Keywords: quorum sensing; Pseudomonas aeruginosa; anti-bacterial; target identification; virulence factor quorum sensing; Pseudomonas aeruginosa; anti-bacterial; target identification; virulence factor





Author: Ysobel R. Baker, Warren R. J. D. Galloway, James T. Hodgkinson and David R. Spring *

Source: http://mdpi.com/



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