A Versatile Cyclic Clickable Platform by Ring-Expansion Metathesis Polymerization: Cyclic Glycopolymers with Lectin-Binding Ability

A new versatile cyclic polymer platform for the design of advanced cyclic materials was prepared by combining ring-expansion metathesis polymerization (REMP) and click chemistry. Cyclic poly(norbornenyl azlactone) backbones were synthesized over an unprecedented length range with number-average degree of polymerization (DP_n) ranging from 25 to 1000. The cyclic topology was thoroughly characterized using ¹H NMR, size exclusion chromatography (SEC) with multiangle light scattering (MALS) and viscometer detection. Postpolymerization modification (PPM) of these scaffolds was carried out with amino-terminated mannoses using the click aminolysis of the azlactone moiety to prepare a library of multivalent cyclic glycopolymers. The binding inhibition of the resulting cyclic glycopolymers was assessed against a panel of model and biologically relevant lectins (Bc2L-A, FimH, langerin, DC-SIGN, and ConA). The cyclic carbohydrate-functionalized polynorbornenes exhibited high lectin-binding inhibitory potency in the biochip assay, surpassing their monovalent analogues by several orders of magnitude and competing strongly with their linear polymer analogues in terms of IC₅₀ values. Interestingly, the cyclic polymers also prevented the adhesion of Adherent-Invasive Escherichia coli implied in Crohn’s disease, to intestinal cells.