The Characterisation and Development of a New Class of Translation-Initiation Inhibitors
Publication Date
July 24, 2020
Creator
Abstract
This thesis describes synthetic methodologies towards monogalactosyldiacylglycerol and their glycolipid variants, an emerging class of translational inhibitors which show significant potential in eliminating proliferatory disease. The Hayes group have identified MGDG 1, a translation- initiation inhibitor which exerts its therapeutic effects through inhibiting eIF4A, a helicase which functions to unwind RNA in the translational stages of synthesis. However, its specific mode of action and binding has not yet been elucidated.
Chapter 1
Provides a comprehensive literature review of previous synthetic routes in the development of mono-galactolipids, with emphasis on methodologies of anomeric induction. Key therapeutic attributes of MGDG are described in this section, followed by a summary of previous optimisation efforts, conducted by the Hayes group in increasing the therapeutic potency of the natural substrate.
Chapter 2
Describes the synthesis of a mono-galactolipid and mono-glycolipid, with future plans to use the molecules in carbene foot-printing studies, in which specific ligand-protein binding interactions can be identified. Optimisation studies in which protecting groups were manipulated, in order to isolate the natural product in elevated yields have been described. Alternative synthetic routes towards the development of natural product, via more convergent routes have been proposed and evaluated. Finally, attempts at synthesising simplified analogues with reduced molecular weight and potentially enhanced water solubility are described.
Item Type
ethesis
Thesis Type
MScRes
Supervisors
Keywords
Subjects (LC)
Associated Schools / Departments
School of Chemistry
eprints ID
59915
UoN Repository URI
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Aamina Final Thesis corrected 3.pdf
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Full-text
Description
Examined. The Characterisation and Development of a New Class of Translation-Initiation Inhibitors
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2.07 MB
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