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http://dx.doi.org/10.1007/s10059-009-0144-6

Development of Inhibitors against TraR Quorum-Sensing System in Agrobacterium tumefaciens by Molecular Modeling of the Ligand-Receptor Interaction  

Kim, Cheoljin (Department of Chemistry, Princeton University)
Kim, Jaeeun (Environment Group, Samsung Advanced Institute of Technology, Samsung Electronics Co.)
Park, Hyung-Yeon (Department of Chemistry, College of Natural Science, Inha University)
Park, Hee-Jin (School of Chemical and Biological Engineering, World Class University (WCU) Program of Chemical Convergence for Energy and Environment, College of Engineering, Seoul National University)
Kim, Chan Kyung (Department of Chemistry, College of Natural Science, Inha University)
Yoon, Jeyong (School of Chemical and Biological Engineering, World Class University (WCU) Program of Chemical Convergence for Energy and Environment, College of Engineering, Seoul National University)
Lee, Joon-Hee (Department of Pharmacy, College of Pharmacy, Pusan National University)
Publication Information
Molecules and Cells / v.28, no.5, 2009 , pp. 447-453 More about this Journal
Abstract
The quorum sensing (QS) inhibitors that antagonize TraR, a receptor protein for N-3-oxo-octanoyl-L-homoserine lactones (3-oxo-C8-HSL), a QS signal of Agrobacterium tumefaciens were developed. The structural analogues of 3-oxo-C8-HSL were designed by in silico molecular modeling using SYBYL packages, and synthesized by the solid phase organic synthesis (SPOS) method, where the carboxamide bond of 3-oxo-C8-HSL was replaced with a nicotinamide or a sulfonamide bond to make derivatives of N-nicotinyl-L-homoserine lactones or N-sulfonyl-L-homoserine lactones. The in vivo inhibitory activities of these compounds against QS signaling were assayed using reporter systems and compared with the estimated binding energies from the modeling study. This comparison showed fairly good correlation, suggesting that the in silico interpretation of ligand-receptor structures can be a valuable tool for the pre-design of better competitive inhibitors. In addition, these inhibitors also showed anti-biofilm activities against Pseudomonas aeruginosa.
Keywords
acyl-homoserine lactones; binding energies (docking score); FlexX docking study; N-nicotinyl-L-homoserine lactones; N-sulfonyl-L-homoserine lactones; quorum-sensing inhibitor; TraR;
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