Lacey E, Edgar J A, Culvenor C C
Biochem Pharmacol. 1987 Jul 1;36(13):2133-8. doi: 10.1016/0006-2952(87)90141-9.
Phomopsins comprise a family of peptide mycotoxins containing a 13-membered ring formed by an ether bridge, produced by the fungus Phomopsis leptostromiformis, the causal agent in lupin poisoning (lupinosis). The biochemical actions of two naturally occurring phomopsins, phomopsin A and B, and the chemical derivatives, phomopsinamine A and octahydrophomopsin A, on purified sheep brain tubulin were investigated. All analogues were potent microtubule inhibitors, blocking the polymerization of tubulin at concentrations of less than 1 microM. They inhibited [3H]vinblastine binding to tubulin and, in common with vinblastine and its competitive inhibitor maytansine, enhanced the binding of [3H]colchicine to tubulin. It is postulated that phomopsin A and its analogues exert their action on tubulin by interaction at or near the vinblastine binding site. Two possible mechanisms for the interaction between vinblastine or phomopsins and colchicine binding to tubulin are proposed.
拟茎点霉毒素是一类肽类霉菌毒素，由真菌拟茎点霉（Phomopsis leptostromiformis，羽扇豆中毒，即羽扇豆病的病原体）产生，其含有一个由醚桥形成的13元环。研究了两种天然存在的拟茎点霉毒素（拟茎点霉毒素A和B）以及化学衍生物（拟茎点霉胺A和八氢拟茎点霉毒素A）对纯化的绵羊脑微管蛋白的生化作用。所有类似物都是有效的微管抑制剂，在浓度低于1微摩尔时可阻断微管蛋白的聚合。它们抑制[3H]长春碱与微管蛋白的结合，并且与长春碱及其竞争性抑制剂美登素一样，增强了[3H]秋水仙碱与微管蛋白的结合。据推测，拟茎点霉毒素A及其类似物通过在长春碱结合位点或其附近相互作用对微管蛋白发挥作用。提出了长春碱或拟茎点霉毒素与秋水仙碱结合微管蛋白之间相互作用的两种可能机制。
