Date of Award

Spring 1-1-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy In Clinical And Bioanalytical Chemistry Degree

Department

Chemistry

First Advisor

Sun, Xue-long

Second Advisor

Aimin Zhou

Third Advisor

Bin Su

Abstract

Cell surface carbohydrates, existing as glycoproteins, glycolipids, and proteoglycans, often serve as receptors to relay critical interactions and trigger crucial signaling events in many biological processes. Glycan recognition is deeply involved in immune surveillance, response and can provide abundant opportunities to discover the molecular mechanism and potential therapeutic or diagnostic approaches for various diseases. Many useful functionalities can be achieved by developing synthetic glycans to mimic natural carbohydrates. Over the recent decade, glycopolymers, polymers with pendant carbohydrates, have continued to prove usefulness in various applications across different scientific disciplines. For example, glycopolymers can be used as biomimetic glycoligands to study protein functions, modify nanomaterials, and target immune cells to yield tailored immune responses toward a desired outcome. In this dissertation, I employed cyanoxyl-mediated free radical polymerization (CMFRP) for a straightforward synthesis of chain-end functionalized N-glycan polymer-based biomimetic glycoligands with the focus on controlling the chain-end functional group, carbohydrate ligand moiety, linkage and density, then demonstrated their various achievable functionalities. With UV-photoactivatable covalent crosslinking chemistry in mind, novel aryl azide chain-end functionalized N-glycan polymers were synthesized for affinity assisted photo-labeling of proteins that are specific to the carbohydrate moieties expressed on the polymer backbone. The synthestic glycopolymers have demonstrated promising v capabilities for specifically labeling proteins and will be useful multivalent ligands for identifying protein targets and their affinity of interest. Secondly, the glycopolymer’s ability to achieve complexation ofsingle-wall carbon nanotubes (SWCNTs) was demonstrated in aqueous environment. Particularly, it was discovered that disaccharide lactose-containing polymers with dense carbohydrate pendent units and long backbones allowed for the best performance, which revealed the synergistic effects of carbohydrate identity and polymer chain length on introducing water solubility to SWCNTs. It was discovered that that the dispersion of SWCNTs with the novel N-glycan polymers yielded even greater water solubility than that with the well-known and conventional dispersant - DNA-(GT)20. Finally, the immunomodulation effects of the novel synthetic N-glycan polymers were compared with model compound, lipopolysaccharide, upon treatment of mouse macrophages using a series of newly developed high-throughput multiplex assays on micropillar chips and 384-pillar plates platforms, which are validated using conventional 96-well plates.

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