Glycopolymers with secondary binding motifs mimic glycan branching and display bacterial lectin selectivity in addition to affinity

Abstract

The application of synthetic glycopolymers to anti-adhesive therapies has so far been limited by their lack of lectin specificity. Here we employ a macromolecular engineering approach to mimic glycan architecture. A new, 3-step tandem post-polymerisation methodology was developed which afforded precise control over both chain length and carbohydrate (galactose)-polymer backbone linker distance. This route also allowed a secondary binding (branched) motif to be introduced onto the linker, increasing specificity and affinity towards bacterial toxins without the need for extensive carbohydrate or organic chemistry. Sequential variation of this motif was found to dramatically alter both the affinity and the specificity of the glycopolymers towards two lectins, CTx and PNA, by up to 20-fold either via direct binding, or increased steric constraints. Using this method, a glycopolymer that showed increased specificity towards CTx was identified.