“Onion peel” dendrimers: a straightforward synthetic approach towards highly diversified architectures

Abstract

We report herein a novel “onion peel strategy” for the divergent construction of glycodendrimers using different building blocks at each layer of the dendritic growth. A combination of successive highly efficient, versatile, and robust chemical reactions, namely thiol–ene or thiol–yne, esterification, and azide–alkyne click chemistry, generated dendrimers having chemically heterogeneous layers, some of which having UV-visible functions. The dendrimers prepared using this strategy are fundamentally different to conventional dendritic systems that are usually built from repetitive building nanosynthons with limited surface groups. The applicability of this novel approach towards the construction of biologically active glycodendrimers having dense surface sugar residues within low dendrimer generations was fully demonstrated using Erythrina cristagalli, a leguminous lectin known to bind natural killer cells through its galactoside recognition ability. The dendrimer's surface was decorated with an azido derivative of N-acetyllactosamine using click chemistry which led to new glycodendrimers having high affinities as compared to the corresponding monovalent analog. The ongoing quest for better parameterization of critical carbohydrate–protein recognition factors necessitates structures with tailored biophysical properties, sizes, and shapes together with optimized tri-dimensional architectures. The proposed methodology, for which entirely orthogonal building blocks can be applied, represents an additional contribution to the wide arsenal of existing strategies which can create higher structural diversity among dendritic structures of biological interest.