河豚毒素(TTX)及其衍生物的电子结构和构效关系及与石房蛤毒素(STX)的比较研究

对河豚毒素(TTX)及其五个衍生物进行了量子化学计算, 根据对其电子结构及相关分析研究结果, 结合其空间结构特点, 讨论了它们的活性部位、作用方式及构效关系, 发现胍基是最重要的正电中心,在与受体作用时发挥接受电子的重要作用; O(17), O(18), O(15),O(21), O(19)等氧原子是供电子的主要负电部位。对TTX与石房蛤毒素(STX)进行了电子结构和空间结构比较, 发现它们具有相似的电子结构特征, 而且主要活性部位在空间位置上基本相互对应。这表明钠离子通道阻断剂在与受体相互作用时具有共同的结构特征和作用方式, 同时也为探讨受体结构提供了有价值的信息。

Studies on electronic structure and structure-activity relationship of tetrodotoxin(TTX) and its analogs and in comparison with saxitoxin(STX)

Tetrodotoxin(TTX) and saxitoxin (STX) are important neurobiological tools because of their selective and high - affinity blockade of the voltage - gated sodium channel of many excitable membranes. In this paper, the semiempirical self - consistent field MO(INDO) calculations have been undertaken for TTX and its analogs. Their active site, way of action and structure - activity relationship have been discussed on the basis of studies of electronic structure and correlative analysis. It is found that the guanidinium group is the most important positive charge center and it may act as an electron acceptor to interact with the receptor. Oxygen atoms such as O(17), O(18), O(15), O(21), O(19) are important negative charge sites as electron donor. The comparison between TTX and STX on electronic structure and space structure has been undertaken and it is found that they have similar electronic structural features, moreover, their important active sites are mutually corresponding on space position. Studies of these results show that the sodium channel blockade has common structural features and way of action when interact with the receptor, thus leading to identical biological effect.