The Characterisation and Development of a New Class of Translation-Initiation Inhibitors

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Murtza, Aamina (2020) The Characterisation and Development of a New Class of Translation-Initiation Inhibitors. MSc(Res) thesis, University of Nottingham.

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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: Thesis (University of Nottingham only) (MSc(Res))
Supervisors: Hayes, Christopher
Keywords: Galactolipids, MGDG, cancer therapy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 59915
Depositing User: murtza, aamina
Date Deposited: 14 Sep 2023 13:29
Last Modified: 14 Sep 2023 13:29
URI: https://eprints.nottingham.ac.uk/id/eprint/59915

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