The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG‐Dendritic GATG Copolymers

Abstract

A general synthetic strategy to polyethylene glycol (PEG)‐dendritic block copolymers of the GATG (gallic acid–triethylene glycol) family is described from commercially available PEG of different molecular weights and architectures. Glycosylation of the resulting azide‐terminated copolymers with fucose by copper‐catalyzed azide–alkyne cycloaddition (CuAAC) afforded a toolbox to study the effect of PEG on the multivalent binding with the lectin UEA‐I by surface plasmon resonance (SPR, on surface) and isothermal titration calorimetry (ITC, in solution). Our results indicate that PEG reduces the affinity of glycodendrimers towards lectins by steric hindrance in a molecular‐weight‐dependent fashion. Great differences were observed as a function of the PEG architecture, with diblock PEG‐dendritic copolymers benefiting from a positive entropic contribution (PEG folding), not seen in the dendritic‐PEG‐dendritic systems. The self‐inflicted steric stabilization of the PEGylated copolymers onto lectin clusters reveals the necessity of additional competitive experiments to fully assess the antiadhesive properties of PEG in biological environments