Rational Molecular Design og Inhibitors against Quorum-Sensing System

초록

New inhibitors of 3CO8 and 3OC12, which act as an initial signal molecule of the quorum sensing (QS) signalling cascade in Agrobacterium tumefaciens and Pseudomonas aeruginosa, respectively, have been developed. The inhibitor candidates were synthesized by substituting the head and tail portion of the native ligands for 3OC8, 3OC12 with a different group, and their docking poses and scores (binding energies) were predicted by the in silico modelling study. The newly designed ligands gave better docking scores than those for the template molecules and good inhibition effects on TraR, LasR activity in the in vivo bioassay. Most of these synthesized compounds were found to be effective as quorum-sensing antagonists. Based on the successful modelling work, we are working on the design of de novo ligands for Staphylococcus aureus