Taming QscR: Synthetic ligands that modulate the quorum sensing control repressor protein in Pseudomonas aeruginosa

ORGN 111

Margrith E. Mattmann, mattmann@chem.wisc.edu1, Grant D. Geske, geske@chem.wisc.edu1, Gregory A Worzalla, gaworzalla@wisc.edu2, and Helen E. Blackwell, blackwell@chem.wisc.edu1. (1) Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave, Madison, WI 53706, (2) Department of Bacteriology, University of Wisconsin-Madison, 420 Henry Mall, Madison, WI 53706
This poster describes our discovery of synthetic modulators of the Quorum Sensing Control Repressor protein (QscR) in the pathogen Pseudomonas aeruginosa. There is significant interest in QscR as a target for quorum sensing interference, as it represses the activity of two well-characterized receptor proteins in P. aeruginosa, LasR and RhlR. The mechanism of this repression, however, is poorly understood. Unlike LasR and RhlR, QscR lacks an endogenous Nacylated- L-homoserine lactone (AHL) ligand that controls its function as a transcriptional activator. Non-native ligands tuning QscR function, therefore, could clarify the role of QscR in P. aeruginosa quorum sensing and lay foundations for the development of novel anti-infective strategies. We have developed efficient syntheses of non-native AHLs and examined their activity using a variety of in vitro assays. These studies have revealed several QscR inhibitors with nanomolar IC50 values. This poster outlines our ongoing studies in this area.
 

Total Synthesis, Materials, Devices and Switches, Molecular Recognition and Self-Assembly, Biologically-Related Molecules and Processes
8:00 PM-10:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Organic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007