Department or Program

Biological Chemistry

Abstract

O-mannosylation involves the covalent linkage of mannose to a serine or threonine residue of a protein. The attaching mannose may then be extended by other monosaccharides, resulting in M1, M2, and M3 classes of glycans. The M1 and M2 glycans are characterized by the extension of mannose by GlcNAc in either a linear or branched manner, respectively, followed by subsequent elongation by galactose. The M3 structure contains at its terminus a Xyl-GlcA disaccharide repeating unit which is crucial for the function of a-dystroglycan, a well characterized mammalian O-mannosylated protein. O-mannosylation is prevalent in transmembrane proteins, and is important in modulating cell-matrix interactions, cell adhesion, and cell-cell signaling. Disruption of O-mannosylation results in various congenital muscular dystrophies termed dystroglycanopathies. The biological importance of glycosylation is well known, but poorly understood due to the variability and heterogeneity of polysaccharides in biological systems. Therefore, chemical synthetic methods can yield homogenous, pure substances which can be used to probe the biological function of specific glycan structures. The purpose of this research is to organically synthesize the building blocks of O-mannosylated glycans, and to use these building blocks to form complete O-mannose oligosaccharides using automated solution phase synthesis. Synthesis of the GlcNAc building block for M1 and M2 glycans and the Xyl building block for M3 glycans will be presented. In addition, the automated solution phase synthesis of several M1 and M2 glycans will be presented.

Level of Access

Restricted: Embargoed [Open Access After Expiration]

First Advisor

Koviach-Cote, Jennifer

Date of Graduation

5-2018

Degree Name

Bachelor of Science

Number of Pages

101

Components of Thesis

1 pdf file

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