7 膜蛋白質との相互作用解明を志向した梯子状ポリエーテルの設計と合成(口頭発表の部)

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Ladder-shaped polyether (LSP) toxins represented by brevetoxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and 6/7/6/6/7/6/6/7/6/6 decacyclic system, based on the convergent method via α-cyano ethers. The ALPs possessing the simple iterative structure with different number of rings would be useful for structure-activity relationship studies on the molecular length. Two series of ALPs were prepared, (i) both sides were functionalized as diols (A series), and (ii) one side remained as diol and the other side was protected as benzyl ethers (B series), and the interaction of these ALPs with TM proteins was evaluated, based on dissociation of glycophorin A (GpA) dimers into monomers. The heptacyclic ether (ALP7B) elicited the most potent activity in the presence of 2% SDS buffer, whereas the decacyclic ether (ALP10A) exhibited intriguing phenomenon to induce precipitation of GpA in a dose-dependent manner, under the low concentration of SDS (0.03%). The different activities among the ALPs can be accounted for by the concept of 'hydrophobic matching' i.e. lengths of the hydrophobic region including the side chains of ALP7B and ALP10A are ca. 25Å, which match the lengths of the hydrophobic region of α-helical TM proteins, as well as the hydrophobic thickness of lipid bilayer membranes.
天然有機化合物討論会の論文
2008-09-01

7 膜蛋白質との相互作用解明を志向した梯子状ポリエーテルの設計と合成(口頭発表の部)

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