Kapp O H, Siemion J, Eckelman W C, Cohen V I, Reba R C
Department of Radiology, University of Chicago, IL 60637, USA.
Recept Signal Transduct. 1997;7(3):177-201.
Models of the m2 muscarinic receptor have been built and acetylcholine and an antagonist of the quinuclidinyl benzilate family docked to the putative active site. We have incorporated aspects of homology, site-directed mutagenesis studies and structure-activity studies of specific lead compounds in the construction of our receptor models with a primary focus on the structure of the binding sites. We have observed a deep pocket binding of 5-BrQNT, suggesting a plausible explanation for the observation that agonists and antagonists do not bind competitively. The results of these computational studies are interpreted within the context of the observed in vitro results. Our goal is to assist in the development of subtype receptor selective radiopharmaceuticals for use in PET and SPECT.
已经构建了M2毒蕈碱受体模型，并将乙酰胆碱和喹核醇基苯甲酸酯家族的拮抗剂对接至假定的活性位点。在构建我们的受体模型时，我们纳入了同源性、定点诱变研究以及特定先导化合物的构效关系研究等方面，主要关注结合位点的结构。我们观察到5-溴喹核酯（5-BrQNT）存在一个深口袋结合现象，这为激动剂和拮抗剂不具有竞争性结合这一观察结果提供了一个合理的解释。这些计算研究结果将在观察到的体外实验结果背景下进行解读。我们的目标是协助开发用于正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）的亚型受体选择性放射性药物。
