Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA.
Langmuir. 2011 Apr 19;27(8):4936-44. doi: 10.1021/la2005166. Epub 2011 Mar 29.
Macrocyclic oligocholates were found in a previous work (Cho, H.; Widanapathirana, L.; Zhao, Y. J. Am. Chem. Soc.2011, 133, 141-147) to stack on top of one another in lipid membranes to form nanopores. Pore formation was driven by a strong tendency of the water molecules in the interior of the amphiphilic macrocycles to aggregate in a nonpolar environment. In this work, cholate oligomers terminated with guanidinium and carboxylate groups were found to cause efflux of hydrophilic molecules such as glucose, maltotriose, and carboxyfluorescein (CF) from POPC/POPG liposomes. The cholate trimer outperformed other oligomers in the transport. Lipid-mixing assays and dynamic light scattering ruled out fusion as the cause of leakage. The strong dependence on chain length argues against random intermolecular aggregates as the active transporters. The efflux of glucose triggered by these compounds increased significantly when the bilayers contained 30 mol% cholesterol. Hill analysis suggested that the active transporter consisted of four molecules. The oligocholates were proposed to fold into "noncovalent macrocycles" by the guanidinium-carboxylate salt bridge and stack on top of one another to form similar transmembrane pores as their covalent counterparts.
大环寡胆酸盐在之前的研究中被发现（Cho，H.；Widanapathirana，L.；Zhao，Y. J. Am. Chem. Soc. 2011, 133, 141-147）可以在脂质膜中彼此堆叠形成纳米孔。这种孔的形成是由亲水分子内部的水分子在非极性环境中强烈聚集的趋势所驱动的。在这项工作中，研究人员发现末端带有胍基和羧酸盐基团的胆酸盐低聚物能够引起亲水分子（如葡萄糖、麦芽三糖和羧基荧光素（CF））从 POPC/POPG 脂质体中流出。胆酸盐三聚体在运输过程中的表现优于其他低聚物。脂质混合测定和动态光散射排除了融合是泄漏的原因。对链长的强烈依赖表明，随机的分子间聚集体不是有效的转运蛋白。当双层膜中含有 30 mol%胆固醇时，这些化合物引发的葡萄糖外排显著增加。Hill 分析表明，活性转运蛋白由四个分子组成。这些低聚物通过胍基-羧酸盐盐桥折叠成“非共价大环”，并彼此堆叠形成类似于其共价类似物的跨膜孔。
