Carbohydrate–lectin recognition of well-defined heterogeneous dendronized glycopolymers: systematic studies on the heterogeneity in glycopolymer–lectin binding

Heterogeneous glycopolymers have received significant interest in the past few years due to their potential properties in enhancing the molecular recognition abilities toward a specific receptor. However, there are limited reports on correlating the type of non-binding sugar residue with its synergistic effects on the affinity to lectin in a complex hetero-multivalent system. To shed more light on the heterogeneity in carbohydrate–lectin recognition, we have designed heterogeneous dendronized glycopolymers presenting α-mannose, β-galactose, and/or β-glucose residues in the side chains, which are synthesized by post-polymerization modification of activated PFPA ester precursor polymers. Tri-functionalized dendronized amines bearing different sugar motifs have been synthesized by a gradient CuAAC reaction, which could serve as a platform for achieving multi-heterogeneous sugar units in a controlled manner. ITC measurements showed that all heterogeneous dendronized glycopolymers demonstrate higher affinities towards Con A as the model lectin compared to their homogeneous dendronized analogues presenting the same number of binding α-mannose units, which further confirmed that the presence of a β-glucose or β-galactose unit as a non-binding sugar motif could produce a synergistic effect on the binding of an α-mannose unit to Con A. Further systematic studies on the heterogeneity in glycopolymer–lectin binding revealed that β-galactose as a non-binding sugar unit could generate a higher synergistic effect on binding with Con A than the β-glucose unit. More intriguingly, ABC-type dendronized glycopolymers bearing α-mannose, β-galactose, and β-glucose residues show higher affinities towards Con A than their dendronized analogues that present only one type of non-binding sugar unit due to a co-synergistic effect. The stronger synergistic effect of this heterogeneity on the interaction between the ABC-type dendronized glycopolymer and Con A may be expressed as the synergism of the secondary and tertiary sugar units that promote the dynamic movement of lectin from the glycopolymer to glycopolymer epitopes. These results provide more evidence that heterogeneity plays a crucial role in glycopolymer–lectin binding.