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Chemical Approaches to Understanding Glycobiology

Yi, Wen
http://rave.ohiolink.edu/etdc/view?acc_num=osu1224529056

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Biochemistry.
Glycans are vital biopolymers found in organisms across all domains of life. They play critical roles in numerous complex biological processes, ranging from mediation of protein folding, stability and trafficking, to molecular recognition by immune cells, viruses and bacteria. Traditional genetic approach has yielded significant insight into glycan functions, but also has limitations. Glycans are not primary gene products; their biosynthesis is not under direct transcriptional control. Disruption of genes encoding glycan biosynthetic enzymes oftentimes causes the impaired synthesis of multiple glycan structures, making the interpretation of mutant phenotypes very difficult or impossible. Recently, chemical approaches are emerging to be powerful alternatives to genetics in the study of glycobiology. In this thesis, the work has been focusing on using chemical approaches to gain a better understanding of cell surface glycan biosynthesis, investigate pathway mechanism and modulate cell surface glycan presentation. Chapter 1 provides a general introduction of glycan functions, bacterial cell surface polysaccharide biosynthesis, and an overview of chemical approaches used in glycobiology. Two most widely used chemical approaches (also the ones used in this thesis) are highlighted: synthesis of structurally defined glycoconjugates to dissect glycan biosynthesis, and use of unnatural sugar analogs to modulate the cell surface glycosylation. Chapter 2 describes the effort to reconstitute bacterial polysaccharide biosynthesis in vitro. Structurally defined oligosaccharide substrates were obtained using chemo-enzymatic synthesis. These substrates were used in vitro to demonstrate sugar polymerization. Polysaccharide chain length modality was generated in this reconstitution system. In Chapter 3, a sugar nucleotide synthetic pathway was engineered, and its promiscuity was exploited to in vivo incorporate unnatural sugar substrates into bacterial polysaccharides to generate modified structures. Selective chemical reactions were carried out in vitro to further elaborate the functional groups appended to the polysaccharides. In Chapter 4, two novel microbial glycosyltrasferases were characterized and applied in the facile synthesis of two types of important human oligosaccharide antigens: T-antigen mimics and human blood group antigens. Finally, Chapter 5 summaries the main results of studies in this thesis and also provides some directions for future studies in each project.
Peng Wang, PhD (Advisor)
Ross Dalbey, PhD (Committee Member)
Donald Dean, PhD (Committee Member)
F. Robert Tabita, PhD (Committee Member)
Biochemistry
glycobiology; polysaccharide; chemical approaches; glycosyltransferase; chemo-enzymatic synthesis of oligosaccharides

Recommended Citations

Citations

  • Yi, W. (2008). Chemical Approaches to Understanding Glycobiology [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1224529056

    APA Style (7th edition)

  • Yi, Wen. Chemical Approaches to Understanding Glycobiology. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1224529056.

    MLA Style (8th edition)

  • Yi, Wen. "Chemical Approaches to Understanding Glycobiology." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1224529056

    Chicago Manual of Style (17th edition)

osu1224529056
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© 2008, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.