Membrane Protein Recognition by Ladder-shaped Polyether Compounds

众所周知，海洋微藻是结构和生物学上有趣的聚酮化合物的丰富来源。其中，maitotoxin （MTX）因其在次生代谢物中分子量最大，达3422 Da，具有极强的致死率（50 ng/kg，小鼠，ip.）而受到化学家和生化学家的关注。通过核磁共振、质谱联用和合成化学等手段对其结构进行了测定。介绍了一种基于碳质子自旋耦合（2,3jc，H）的非环侧链构型测定新方法。基于这些数据，整个分子的立体结构已被阐明，从而揭示了其分子作用方式。最近的研究结果表明，MTX通过疏水多环醚（结构的上半部分）识别其目标蛋白，这可能与蛋白质的跨膜部分相互作用。

Marine microalgae are known to be arich source of structurally and biologically intriguing polyketides. Among those, maitotoxin (MTX) attracts attention of chemists and biochemists since the toxin possesses the largest molecular weight of 3422 Da among secondary metabolites and very potent lethality (50 ng/kg, mice, ip.). Its structure has been determined by combined use of NMR,MS/MS and synthetic chemistry. A new method based on carbon-proton spin coupling (2,3JC,H) was introduced for the configurational determination of the acyclic sidechains. Based on these data, the stereostructure of the whole molecule has been elucidated, which sheds light on its molecular mode of action. Recent findings suggest that MTX recognaizes its taget protein with the hydrophobic polycyclic ethers (the upper half of the structure), which probably interacts with the transmembrane portion of the protein.