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

Abstract

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.