Multivalent Homo and Hetero Glycodendrimers Allow Sequence-Defined Carbohydrate-Protein Interactions

Abstract

We present the synthesis of multivalent glycodendrimers in homo and hetero patterns utilizing different mannose and galactose carbohydrate residues. Highly efficient mannose thiophenol donor in presence of promoter and linker is the key step to generate a library of mono, di and tri α(1-2) mannose glycans in one-pot method. Introduction of these carbohydrate ligands on a tripodal backbone in stoichiometric ratio allows for the straightforward ynthesis of multivalent hetero and homo glycodendrimers. Surprisingly, all hetero glycodendrimers show high affinities toward Concanavalin A lectin receptors in comparison to their homo-analogs. Detailed studies of E.coli ORN 178 binding further demonstrated the significance of heterogeneity in the glycodendrimers, which promote steric shielding of the glycans to modulate the binding avidity. Overall, these results shed light to the cell surface carbohydrate-protein interactions, which is heterogeneous in nature.