Elucidating the mechanism of ion transport through membranes mediated by CyPLOS, amphiphilic cyclic oligosaccharides

Ion transport through membranes is a vital function, in which different ionophore systems, either carriers or channels, operate adopting finely regulated mechanisms to transport ions into cells. Among the synthetic ionophores, carbohydrate-based molecules have received great consideration, due to their biocompatibility, multifunctionality, and ease of manipulation. In this frame, some of us recently synthesized a cyclic disaccharide named CyPLOS (Cyclic Phosphate-Linked OligoSaccharide), able to discharge a pH gradient across membranes in less than 20 min at 2 wt% ionophore conc. In order to investigate by EPR the mechanism of action through membranes of this ionophore, the spin labeled analog, carrying one TEMPO residue, has been ad hoc synthesized. The EPR data clearly indicate 2 to be active in a monomeric form, with the polar macrocyclic head lying on the surface and the TEG chains deeply inserted in the phospholipid bilayer, which is thus strongly destabilized.