Hydrophilic and Clickable Poly(oxa)norbornenes for Multivalent Lectin Binding

Abstract

Dicarboximide-based poly(oxanorbornenyl azlactone) and poly(norbornenyl azlactone), differing only in the substitution of an oxygen atom for a carbon atom, were obtained by ring-opening metathesis polymerization (ROMP). These well-defined azlactone-functionalized poly(oxa)norbornenes were post-modified via click aminolysis of the azlactone moiety with hydrophobic amino-heptyl mannose, producing glycopolymers with number-average degree of polymerization (DPn-) values of 140 and 25. Notably, the oxygenated dicarboximide-based poly(oxanorbornenyl azlactone) scaffolds exhibited enhanced solubility compared to their norbornenyl analogues. Inhibition tests against five therapeutically relevant lectins (FimH, Bc2L-A, ConA, DC-SIGN, and Langerin) demonstrated nanomolar inhibitions and strong multivalent effects for all polymers, with better lectin binding observed for oxygenated backbone at DPn- = 25. This work highlights that dicarboximide-based poly(oxanorbornenyl azlactone) is a promising platform for the development of highly functional water-soluble glycomaterials with precise structural control.