Mechanistic study on the Bradykinin B1 receptor

缓激肽B1受体（BradykininB1 receptor，B1R）属于GPCR家族，在疼痛和炎症的病理生理过程中起重要作用。基于这些原因，我们的目标是阐明B1R的作用机制。首先，我们构建了B1受体的结构模型。然后，将velutinol A对接到B1受体模型中，然后通过分子动力学计算进行能量最小化和结构优化。从这个对接模拟，我们可以预测的重要取代基velutinol A的结合B1R。另一方面，我们也开始了Velutinol A的合成。最后合成了关键中间体，为后续的合成和构效关系研究奠定了基础。目前我们正在推进Velutinol A及其类似物的全合成，以研究B1R的作用机制。

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.