Heterolayered hybrid dendrimers with optimized sugar head groups for enhancing carbohydrate–protein interactions

Abstract

The efficient synthesis of multifunctional dendrimers lies at the heart of nanomolecular therapeutic applications and constitutes one of the cornerstones of drug and gene delivery. Additional applications of glycodendrimers, in particular, exploit their capacity to block bacterial and viral adhesion mechanisms, including the inhibition of biofilms. We describe here a novel strategy that combines the versatility of the recently discovered construction of “onion peel” (heterolayered) dendrimers with the incorporation of surface hybrid carbohydrate ligands for targeting multiple bacterial strains. We relied on current click reactions, namely, Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAc) and the photolytic thiol–ene reaction using orthogonally functionalized scaffolds. Two families of glycodendrimers were thus synthesized using a convergent strategy. Cyanuric chloride, pentaerythritol, and hexachlorocyclophosphazene were chosen for the different layers. The dendrimers were formed to incorporate both optimised β-D-galactopyranoside and α-D-mannopyranoside ligands. The resulting hybrid glycodendrimers were successfully tested against two different lectins using dynamic light scattering (DLS).