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

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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.