Enhanced Concanavalin A Binding to Preorganized Mannose Nanoarrays in Glycodendrimersomes Revealed Multivalent Interactions
Nina Yu. Kostina, Dominik Söder, Tamás Haraszti, Qi Xiao, Khosrow Rahimi, Benjamin E. Partridge, Michael L. Klein, Virgil Percec, César Rodriguez‐Emmenegger
Abstract
The effect of the two-dimensional glycan display on glycan-lectin recognition remains poorly understood despite the importance of these interactions in a plethora of cellular processes, in (patho)physiology, as well as its potential for advanced therapeutics. Faced with this challenge we utilized glycodendrimersomes, a type of synthetic vesicles whose membrane mimics the surface of a cell and offers a means to probe the carbohydrate biological activity. These single-component vesicles were formed by the self-assembly of sequence-defined mannose-Janus dendrimers, which serve as surrogates for glycolipids. Using atomic force microscopy and molecular modeling we demonstrated that even mannose, a monosaccharide, was capable of organizing the sugar moieties into periodic nanoarrays without the need of the formation of liquid-ordered phases as assumed necessary for rafts. Kinetics studies of Concanavalin A binding revealed that those nanoarrays resulted in a new effective ligand yielding a ten-fold increase in the kinetic and thermodynamic constant of association.