2009 Fiscal Year Final Research Report

Mechanistic study on the Bradykinin B1 receptor

Research Project

Project/Area Number	20710172
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Living organism molecular science
Research Institution	Nigata University of Phermacy and Applied Life Sciences
Principal Investigator	TAMIYA Minoru Nigata University of Phermacy and Applied Life Sciences, 応用生命科学部, 助教 (10468960)
Project Period (FY)	2008 – 2009
Keywords	有機合成 / コンピュータシミュレーション
Research Abstract	The Bradykinin B1 receptor (B1R), belonging to GPCR family, plays an important role in the pathophysiological process of pain and inflammation. Because of these reasons, we aimed to the clarification of the mechanism of action of B1R. First, we constructed the structural models of the B1 receptor. Then, velutinol A was docked in the models of the B1 receptor, followed by energy-minimization and structure-optimization with molecular dynamic calculations. From this docking simulation, we could anticipate the important substituent of velutinol A for the binding to B1R. On the other hand, we have also started the synthesis of velutinol A. Finally we could synthesize the key intermediate for the following synthesis and SAR study. Now we are pushing on the total synthesis of velutinol A and its analogs for the study of mechanism of action of B1R.