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Title: Biological investigation of glycosylated macromolecular structures
Author: De Munari, Sonia
ISNI:       0000 0004 6346 6027
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Carbohydrates play a key role in many biological processes. The complex pool of information that these structures are able to express forms the glycocode. Our understanding of this language is limited, due to the complexity of the sugar structures and the diversity of their functions. The work presented in this thesis aims to contribute to our knowledge of their biological significance by building what we will call a Glycomap, a selection of biologically relevant sugars specifically picked to map the in vivo interactions of carbohydrates and explore some of their applications to different macromolecules: proteins, nanoparticles and carbon nanotubes. The controlled glycosylation of proteins still represents a challenge, hence we decided to exploit the ability to diversify carbohydrates from a common precursor, and developed three glycosylating reagents which allowed the use of different glycosylation strategies on different protein structures. In order to follow the in vivo distribution of the selected carbohydrates, we activated them into the 2-imino-2-methoxyethyl derivatives and used them to decorate amino-functionalised magnetic nanoparticles. These nanoparticles were isolated from different tissues after testing in animal models, and their distribution was recorded. As sugars can also be applied to drug delivery systems as targeting agents, we explored the potential of glycosylated carbon nanotubes in the delivery of radionuclides for imaging and radiotherapeutic purposes. Single-walled carbon nanotubes were filled with a radionuclide and after proper functionalisation decorated with different sugars to deliver them to different targets. Finally, we dedicated one last section to the design of functionalised fullerenes as support for the solid-phase synthesis of oligosaccharides. Fullerene derivatives are able to perform homogenous solution phase synthesis with all the advantages of a solid-phase work-up through precipitation. In this thesis we touched several aspects of carbohydrate synthesis, manipulation and applications, to provide new tools which will help elucidate the role of carbohydrates in biological systems.
Supervisor: Davis, Benjamin Guy Sponsor: EU FP7-ITN Marie-Curie Network programme RADDEL ; EU FP7-Integrated Infrastructure Initiative programme ESTEEM2
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available