Cyclic phosphate-linked oligosaccharides (CyPLOS): Novel carbohydrate-based synthetic ion transporters

Abstract

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 carbohydrate-based macrocycles having the glucoside units connected through 4,6-linked phosphodiester linkages, named CyPLOS (cyclic phosphate-linked oligosaccharides). The cyclic dimer was then adopted as a versatile synthetic platform to obtain a variety of analogs, carrying long linear alkyl or polyether chains. Diverse, jellyfish-shaped amphiphilic CyPLOS were thus obtained, with the compound carrying four tetraethylene glycol (TEG) tentacles acting as good ion transporter through lipid bilayers. A fine tuning of the properties and complexation abilities of these amphiphilic analogs was realized by introducing special reporter groups at the extremities of the TEG tentacles. Through the design of an azido-TEG functionalized key intermediate, a fluorescently labeled CyPLOS derivative was synthesized, showing a markedly increased ionophore activity, with the fluorescent tag also allowing the investigation of its mechanism of action and localization within the phospholipid bilayers. Incorporation of a spin label at the CyPLOS tentacles—to provide further insight into the study of their interactions with phospholipid membranes by electron spin resonance (ESR) spectroscopy—was also profitably achieved through a postsynthetic functionalization approach.