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Molecules 2013, 18(10), 11783-11796; doi:10.3390/molecules181011783
Communication

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

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Received: 5 August 2013; in revised form: 9 September 2013 / Accepted: 17 September 2013 / Published: 25 September 2013
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
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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.
Keywords: quorum sensing; Pseudomonas aeruginosa; anti-bacterial; target identification; virulence factor quorum sensing; Pseudomonas aeruginosa; anti-bacterial; target identification; virulence factor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Baker, Y.R.; Galloway, W.R.J.D.; Hodgkinson, J.T.; Spring, D.R. 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. Molecules 2013, 18, 11783-11796.

AMA Style

Baker YR, Galloway WRJD, Hodgkinson JT, Spring DR. 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. Molecules. 2013; 18(10):11783-11796.

Chicago/Turabian Style

Baker, Ysobel R.; Galloway, Warren R.J.D.; Hodgkinson, James T.; Spring, David R. 2013. "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." Molecules 18, no. 10: 11783-11796.


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