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

dc.contributor.authorBianculli, Rachel Helenen
dc.contributor.committeechairSchulz, Michaelen
dc.contributor.committeememberEdgar, Kevin J.en
dc.contributor.committeememberGandour, Richard D.en
dc.contributor.committeememberMatson, Johnen
dc.contributor.departmentChemistryen
dc.date.accessioned2025-06-06T08:02:38Zen
dc.date.available2025-06-06T08:02:38Zen
dc.date.issued2025-06-05en
dc.description.abstractThis 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.en
dc.description.abstractgeneralInfluenza is a major health concern worldwide. Currently, vaccines are the primary way to prevent influenza infections and pandemics, but they suffer from several limitations. Antiviral drugs have also been designed to target influenza, but because influenza constantly mutates into new strains, many antiviral medications can quickly be rendered ineffective. Antiviral polymers—materials that can mimic the interactions between cells and viruses—may serve as an alternative class of therapeutic. Polymers, due to their highly repetitive structure, can act as molecular "Velcro" across influenza's surface, reducing the number of available binding sites for replication and consequently reducing infection. We synthesized a library of sialic acid-containing copolymers that would mimic influenza's well-studied virus-cell interactions. Previous anti-influenza polymers also used sialic acid to induce inhibition, however, broad conclusions from this work are often difficult to draw due to conflicting data, non-uniform experimental conditions, and varied structural motifs. Our research aims to design a synthetic platform capable of systematically varying polymer properties and applying it to sialic acid-containing materials. By creating large libraries with systematic variation, we can study how small structural changes impact the efficacy of inhibition and further elucidate the mechanism of inhibition. Though this work focuses on influenza inhibition, these polymers could also be studied for a variety of viruses that use sialic acid as a binding receptor.en
dc.description.degreeDoctor of Philosophyen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:41600en
dc.identifier.urihttps://hdl.handle.net/10919/135091en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectSialic aciden
dc.subjectGlycomaterialsen
dc.subjectPost Polymerization Modificationen
dc.subjectReversible Addition Fragmentation Chain Transfer (RAFT) polymerizationen
dc.subjectAntiviralen
dc.subjectPolyvalencyen
dc.titleA Systematic Study of Sialic-Acid-Containing Poly(styrene sulfonate) for Antiviral Applicationsen
dc.typeDissertationen
thesis.degree.disciplineChemistryen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.nameDoctor of Philosophyen

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