Double-Modified Glycopolymers from Thiolactones to Modulate Lectin Selectivity and Affinity

Multivalent glycomaterials show high affinity toward lectins but are often nonselective as they lack the precise 3-D presentation found in native glycans. Here, thiolactone chemistry is exploited to enable the synthesis of glycopolymers with both a primary binding (galactose) and a variable secondary binding unit in close proximity to each other on the linker. These polymers are used to target the Cholera toxin B subunit, CTxB, inspired by its native branched glycan target, GM-1. The secondary, nonbinding unit was shown to dramatically modulate affinity and selectivity toward the Cholera toxin. These increasingly complex glycopolymers, assembled using accessible chemistry, can help breach the synthetic/biological divide to obtain future glycomimetics.