Hydrogen bond-assisted macrocyclic oligocholate transporters in lipid membranes

• Published in: Organic & biomolecular chemistry 2012-07, Vol.10 (26), p.5077-5083
• Main Authors: Widanapathirana, Lakmini, Li, Xueshu, Zhao, Yan
• Format: Article
• Language: English
• Subjects: Biological Transport; Carboxylic Acids - chemistry; Carboxylic Acids - metabolism; Cholates - chemistry; Cholates - metabolism; Fluoresceins - metabolism; Glucose - metabolism; Guanidine - chemistry; Guanidine - metabolism; Hydrogen Bonding; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - metabolism; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; Unilamellar Liposomes - chemistry; Unilamellar Liposomes - metabolism
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c2ob25301a

Three macrocyclic oligocholates containing a carboxyl group, a guanidinium ion, and a Cbz-protected amine, respectively, were studied as membrane transporters for hydrophilic molecules. To permeate glucose across lipid bilayers, the macrocycles stacked over one another to form a transmembrane nanopore, driven by a strong tendency of the water molecules in the internal cavities of the amphiphilic macrocycles to aggregate in a nonpolar environment. To transport larger guests such as carboxyfluorescein (CF), the macrocycles acted as carriers to shuttle the guest across the membrane. Hydrogen-bonds between the side chains of the macrocycles strongly affected the transport properties. Surprisingly, the carboxyl group turned out to be far more effective at assisting the aggregation of the oligocholate macrocycles in the membrane than the much stronger carboxylate-guanidinium salt bridge, likely due to competition from the phosphate groups of the lipids for the guanidinium.