Chemoenzymatic Preparation of Probes for in vitro and Cellular Elucidation of Complex Bacteria Polysaccharides

1 online resource (151 pages) : PDF

2021

University of North Carolina at Charlotte

Bacteria play a major role in our health and wellbeing. The microbe-host interaction is often mediated by sugar polymers at the cell surface. An incredibly diverse amount of glycan variation exists throughout these structures, which makes identification of surface components difficult. The composition of the surface is unique to bacteria and acts as molecular fingerprint which can distinguish even subspecies apart. Better methods to decipher what those glycan identities are or how to reproduce them may help develop future advancements towards exploiting them as therapeutic targets. The major challenge addressed herein is to simplify the tools used to track the formation of these natural materials. To do this, we expand on the chemoenzymatic preparation of a tagged lipid substrate central to early stages of biosynthesis for many surface polysaccharides. Further, we identify conditions in which these unnatural substrates can be used in vitro. Lastly, we develop methodologies to detect BP and polysaccharide intermediates in live cells. These tools have facilitated robust detection and reconstruction of glycan assembly building blocks. This research may lay the ground work for future applications technologies towards novel therapeutics, such as glycoconjugates vaccines.

doctoral dissertations

Microbiology
Biochemistry
Analytical chemistry

Ph.D.

Bactoprenyl Diphosphate
Glycan Immobilization
Initiating Glycosyltransferases
Lipid Linked Oligosaccharides
Polyisoprenoids
Undecaprenyl Diphosphate Synthase

Nanoscale Science

Troutman, Jerry

Ogle, Craig
Nesmelov, Yuri
De Silva Indrasakara, Swarnapali
Clemens, Mark

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2021.

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Reid_uncc_0694D_12676

http://hdl.handle.net/20.500.13093/etd:2052