CyPLOS, a new family of synthetic ion transporters

Artificial ion transporters are synthetic molecules mimicking at a functional level the activity of naturally occurring ion channels or carriers. In the frame of cyclodextrin mimicry, we recently described the synthesis and conformational properties of new oligosaccharide-based macrocycles having the glucoside units connected through phosphate linkages, named CyPLOS (Cyclic Phosphate-Linked Oligosaccharides). The cyclic disaccharide was adopted as a suitable synthetic platform to obtain a variety of analogues, carrying long alkyl or polyether chains, so to result into diverse jellyfish-shaped amphiphilic CyPLOS. Some compounds in the investigated series were found to be good ion transporters through lipid bilayers. For a fine tuning of the properties and complexation abilities of these macrocycles, a special reporter group is desirable at the extremities of the tentacles, so to insert ad hoc selected appendages (as fluorescent, hydrophobic or electrochemical probes). Through the design of a versatile glucoside key intermediate, bearing terminal azido groups useful in several coupling schemes, a new, fluorescently-labelled CyPLOS analog has been synthesized, found to be a more active ion transporter than the previously prepared congeners and allowing a detailed investigation on its mechanism of action and localization within the phospholipid bilayers.