A Systematic Study of Sialic-Acid-Containing Poly(styrene sulfonate) for Antiviral Applications

Abstract

This dissertation presents the development of a versatile and modular synthetic platform for constructing functional copolymers using post-polymerization modification (PPM) of activated esters. By decoupling the synthesis of the polymer backbone from the introduction of functional groups, this strategy enables precise and efficient tuning of key polymer features (degree of polymerization, functionality, and hydrophobicity). While PPM has been widely used for homopolymers, this work extends its application to copolymers, offering a powerful tool for studying how subtle variations in polymer structure influence performance in biological applications. To demonstrate the platform's utility, it was applied to develop and study antiviral polymers that mimic the binding receptor commonly exploited by influenza viruses to initiate infection, sialic acid. Through systematic variation of polymer parameters, libraries of styrene-sulfonate sialic acid-containing copolymers with covaried degree of polymerization and sialic acid content were synthesized and evaluated for their inhibition of influenza through various virological assays. The modular design of the synthetic platform enables isolation of individual polymer parameters, with preliminary assay data indicating that comonomer identity has a greater impact on antiviral efficacy than either sialic acid content or degree of polymerization alone. While this work focused on influenza, the materials and synthetic strategies developed here could be adapted for other sialic acid-binding pathogens, laying the groundwork for broader antiviral polymer design.