Martyn, Benjamin T. (2017) Glycosylated materials to probe the role of heterogeneity. PhD thesis, University of Warwick.

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Abstract

Identifying and treating infectious diseases remains a challenge for modern healthcare professionals. Proper identification of infectious diseases and understanding of the means of infection will allow for optimal use of antibiotics and the development of alternative therapies such as anti-adhesion therapy. It is therefore important to develop tools that can probe the processes involved in infection, or that can be used as point of care diagnostics. In vivo glycosylated surfaces are inherently heterogeneous, increasing the complexity of the interactions that take place, and with a corresponding increase in analytical difficulty. Glycopolymers and glycosylated nanoparticles are ideal methods for incorporating synthetic functionalisation into a biological setting to probe interactions between glycosylated surfaces and carbohydrate recognising proteins (lectins).

This work utilises heterogeneously glycosylated polymers to probe the inhibitory and kinetic activity of the polymers towards various lectin targets. We see further evidence of the “heterocluster effect” whereby nominally non-binding sugar epitopes give rise to faster association rates and increase overall residence time of bound lectins to the polymers. Highly coloured heterogeneously glycosylated gold nanoparticles are used to develop a high throughput screening library for the identification of binding patterns with lectins that could lead to use as an identification system of unknown lectins. Finally, unnatural azide containing sugars are used to metabolically label the surface of A549 carcinoma cells and tagged using fluorescent polymers. This system provides a robust way of introducing polymeric functionality onto the surface of cells, opening the ability to probe in-depth the cell surface.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH):	Communicable diseases, Glycoproteins -- Immunology, Carbohydrates -- Immunology, Proteins -- Immunology, Glycoconjugates -- Synthesis
Official Date:	October 2017
Dates:	Date Event October 2017 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Gibson, Matthew I.
Format of File:	pdf
Extent:	xxv, 265 leaves : illustrations, charts
Language:	eng

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