Sagara T, Egashira H, Okamura M, Fujii I, Shimohigashi Y, Kanematsu K
Institute of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Bioorg Med Chem. 1996 Dec;4(12):2151-66. doi: 10.1016/s0968-0896(96)00219-2.
For three-dimensional understanding of the mechanisms that control potency and selectivity of the ligand binding at the atomic level, we have analysed opioid receptor-ligand interaction based on the receptor's 3D model. As a first step, we have constructed molecular models for the multiple opioid receptor subtypes using bacteriorhodopsin as a template. The S-activated dihydromorphine derivatives should serve as powerful tools in mapping the three-dimensional structure of the mu opioid receptor, including the nature of the agonist-mediated conformational change that permits G protein-coupling to "second messenger' effector molecules, and in identifying specific ligand-binding contacts with the mu opioid receptor. The analyses of the interactions of some opioid ligands with the predicted ligand binding sites are consistent with the results of the affinity labeling experiments.
为了从原子水平三维理解控制配体结合效力和选择性的机制，我们基于受体的三维模型分析了阿片受体 - 配体相互作用。第一步，我们以细菌视紫红质为模板构建了多种阿片受体亚型的分子模型。S - 活化二氢吗啡衍生物应可作为强大工具，用于绘制μ阿片受体的三维结构，包括激动剂介导的构象变化的性质，这种变化允许G蛋白与“第二信使”效应分子偶联，以及用于识别与μ阿片受体的特定配体结合接触点。一些阿片类配体与预测的配体结合位点相互作用的分析结果与亲和标记实验的结果一致。
