亮氨酸脑啡肽的电子结构及构效关系研究

THE STUDIES ON ELECTRONIC STRUCTURE AND STRUCTUREACTIVITY RELATIONSHIPS OF [LEU^5]-ENKEPHALIN

对亮氨酸脑啡肽进行了量子化学(INDO)计算,研究其电子结构特征,讨论其活性部位、作用机理及构效关系。同吗啡和R31833进行了活性部位的电子结构与空间结构比较,推断它们的活性药效结构具有共同特点,与阿片受体相互作用时作用方式相同,作用部位有对应关系,因而具有相同的药理性质。

The quantum chemical (INDO) calculations have been undertaken for [Leu^5]-enkephalin. The electronic structure was investigated, the active site, the way of action and structure-activity relationship were discussed. It was found that the region of N(1) is the main active site for acceptance of electron, the region of O(51) and O(52) is the main active site for providing electron when interacting with the opiate receptor. [Leu^5]-enkephalin was compared with morphine and R31833 in electronic and spatial structure of active site. Study of the results showed that the N (1) in [Leu^5]-enkephalin corresponds to the N in morphine and the N (9) in R31833, phenyl of Tyr^1 in [Leu^5]-enkephalin corresponds to the phenyl in morphine and the phenyl of phenylethyl in R31833, the O(51) and O(52) in [Leu^5]-enkephalin corresponds to the O(3) in morphine and the O(25) in R31833, the O(4) in [Leu^5]-enkephalin corresponds to the O(29) or O(27) in R31833. On the basis of these studies, it was inferred that these compounds have common feature in pharmacophore. They not only have the same way of action but also have common site of action in the receptor when they interact with the opiate receptor.