Gawley R E, Rein K S, Kinoshita M, Baden D G
Department of Chemistry, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Coral Gables, FL 33124-0431.
Toxicon. 1992 Jul;30(7):780-5. doi: 10.1016/0041-0101(92)90014-v.
The marine toxins known generically as brevetoxins, as well as their structural relative ciguatoxin, are known as polyether ladder toxins, and bind uniquely to site 5 of the voltage-sensitive sodium channel. Rat brain synaptosome binding data show similarities in binding affinity for brevetoxins having the same structural (ladder) backbone, but different affinities between brevetoxins having different backbones. Ciguatoxin has a different backbone from the brevetoxins, but binds even more strongly to the same site. Could the flexibility of the backbone be related to their relative toxicities? As part of an effort to identify the common pharmacophore for the toxins, Monte Carlo methods were used to generate conformational models of the polyether ladder toxin brevetoxin B (PbTx-2) which shows significant flexibility at the juncture of the two 7-membered rings.
一般被称为短裸甲藻毒素的海洋毒素，以及它们的结构类似物雪卡毒素，被称为聚醚阶梯毒素，它们独特地结合于电压敏感钠通道的位点5。大鼠脑突触体结合数据显示，具有相同结构（阶梯）主链的短裸甲藻毒素在结合亲和力上存在相似性，但不同主链的短裸甲藻毒素之间的亲和力不同。雪卡毒素与短裸甲藻毒素的主链不同，但与相同位点的结合更强。主链的灵活性是否与它们的相对毒性有关？作为确定毒素共同药效基团工作的一部分，采用蒙特卡罗方法生成了聚醚阶梯毒素短裸甲藻毒素B（PbTx - 2）的构象模型，该毒素在两个七元环的连接处显示出显著的灵活性。
