Electronic Theses and Dissertations

Date of Award

1-1-2021

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Joshua S. Sharp

Second Advisor

Joshua S. Sharp

Third Advisor

Kristie Willett

Relational Format

dissertation/thesis

Abstract

Heparin and heparan sulfate (Hp/HS) are linear complex glycosaminoglycans (GAGs), which are involved in diverse biological processes. Although Hp/HS GAGs influence numerous physiological and pathophysiological processes, their high degree of size polydispersity and sequence microheterogeneity make structure-function characterization challenging. In addition, it is hard to understand the structures that underlie any of the various functions with MS, because of the lability of the sulfate group during tandem mass spectrometry (MS/MS) analysis. The work presented here describes an in-depth approach for functional oligosaccharide characterization including chemical derivatization of Hp to inhibit COVID-19 infection, multi-dimensional liquid chromatography (LC) fractionation method, chemical derivatization coupled with LC-MS/MS sequencing method, and MS-based fast photochemical oxidation of carbohydrates (FPOC) for glycan-protein interaction study. Collectively, the work provides efficient strategies to recognize the complex Hp/HS structure-function relationships, gaining more complete knowledge of glycomics. ?

Available for download on Wednesday, December 14, 2022

Share

COinS