Date of Award
Spring 5-6-2019
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Peng George Wang
Second Advisor
Jenny Yang
Third Advisor
Gregory Poon
Abstract
Locating at the outer surface of cells, glycans and their glycoconjugates play multitude of roles in biological processes. Among these, protein O-GlcNAcylation is involved in a variety of age related diseases, such as Alzheimer’s disease, diabetes, and cancer development. O-GlcNAc cycling is catalyzed by only two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), raising key questions regarding the regulation and selectivity of these enzymes. In project one, we synthesized a series of glycopeptide substrates with various GlcNAc derivatives to study the specificity of human OGA. Several sugar moieties were discovered to be resistant to OGA hydrolysis which had the potential to be used as O-GlcNAcylation probes through metabolic glycan labeling (MGL).
Installation of an antibody-recruiting moiety on the surface of disease-relevant cells can lead to the selective destruction of targets by the immune system. Herein, in project two, taking advantage of MGL strategy, we synthesized the folic acid-azidosugar conjugate and described the development of a new strategy to selectively deliver azidosugar and introduce L-rhamnose antigens via click chemistry onto cancer cell surface. The immune system can be further activated by the installed antigens to clear out cancer cells. Such an approach can be an alternative and potential strategy to traditional chemotherapeutics in cancer therapy and possibly other diseases.
Carbohydrate-protein interactions are essential for body function, but implicated to capture and identify. In project three, we aim to develop a novel method to lock carbohydrate-protein interactions in a covalent form. Expanding the genetic code to incorporate crosslinkers into proteins enables us capture and identify unknown glycoproteins, manipulate carbohydrate-protein interactions, and study the glycan-related downstream biological signaling.
DOI
https://doi.org/10.57709/14223779
Recommended Citation
Li, Shanshan, "Applications of Glycoconjugates for Enzyme Substrate Specificity Exploration, Immune Therapy, and Carbohydrate-Protein Interaction Study." Dissertation, Georgia State University, 2019.
doi: https://doi.org/10.57709/14223779