Synthetic studies of the hydrophobic part of maitotoxin for elucidating its target proteins

Maitotoxin（MTX）是一种巨大的阶梯状聚醚，具有很强的生物活性。由于天然来源的材料供应不足，其靶蛋白和分子水平上的调节仍然未知。基于MTX的整个结构不需要引起生物活性的假设，我们开发了抑制MTX诱导的生物活性的拮抗剂。我们设计并合成了与疏水部分（W-C′）相对应的部分MTX结构和具有七环体系的人工阶梯型聚醚（ALP）。我们发现W-C′抑制mtxind诱导的溶血活性，而ALP分别抑制mtxind诱导的大鼠胶质瘤C6细胞的Ca2+内流，具有迄今报道的最有效的抑制活性。

Maitotoxin(MTX) is a gigantic laddershaped polyether which possesses potent biological activities. Its target proteins and modeofaction at the molecular level remain unknown due to the short supply of materials from natural sources. Based on our hypothesis that whole structure of MTX is not necessary to elicit the biological activities, we developed antagonists that inhibit the biological activities induced by MTX. We designed and synthesized a partial MTX structure corresponding to the hydrophobic portion(W-C'), and an artificial laddershaped polyether(ALP) possessing heptacyclic ring systems. We have found that W-C' inhibited MTXinduced hemolytic activity, whereas the ALP inhibited MTXinduced Ca2+ influx in rat glioma C6 cells, respectively, with most potent inhibitory activities that have ever been reported.