ROMP-based Glycopolymers with High Affinity for Mannose-Binding Lectins

Well-defined, highly reactive poly­(norbornenyl azlactone)­s of controlled length (number-average degree of polymerization D P n ̅ = 10 to 1,000) were made by ring-opening metathesis polymerization (ROMP) of pure exo-norbornenyl azlactone. These were converted into glycopolymers using a facile postpolymerization modification (PPM) strategy based on click aminolysis of azlactone side groups by amino-functionalized glycosides. Pegylated mannoside, heptyl-mannoside, and pegylated glucoside were used in the PPM. Binding inhibition of the resulting glycopolymers was evaluated against a lectin panel (Bc2L-A, FimH, langerin, DC-SIGN, ConA). Inhibition profiles depended on the sugars and the degrees of polymerization. Glycopolymers from pegylated-mannoside-functionalized polynorbornene, with D P n ̅ = 100, showed strong binding inhibition, with subnanomolar range inhibitory concentrations (IC50s). Polymers surpassed the inhibitory potential of their monovalent analogues by four to five orders of magnitude thanks to a multivalent (synergistic) effect. Sugar-functionalized poly­(norbornenyl azlactone)­s are therefore promising tools to study multivalent carbohydrate–lectin interactions and for applications against lectin-promoted bacterial/viral binding to host cells.