Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.804795
Title: The design and synthesis of molecular tools for probing biological function
Author: Milne, Kirsty
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2020
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Abstract:
With the pharmaceutical industry becoming more interested in exploiting protein-protein interactions, the technique of peptide stapling has become more common. Current strategies either exploit the reactivity of naturally occurring side chains such as glutamic acid, lysine and cysteine, or employ a ring-closing metathesis of either functionalised natural amino acids or unnatural, unsaturated hydrocarbon amino acid staples, such as Fmoc S5, placed at strategic points in the sequence. However, functionalised hydrocarbon amino acid staples are essentially unknown, particularly those which are fluorinated. Fluorination is a commonly employed strategy for both small molecules and peptides. Thus, combining both peptide stapling, and fluorination could bring a valuable contribution to the world of peptide synthesis by potentially improving the strength of protein-protein interactions and providing a useful method of measuring interactions The first chapter of this thesis contains several routes for the synthesis of 3,3- difluoro-5-iodopent-1-ene (1.140), a key intermediate on the pathway to a fluorinated Fmoc S5 analogue. Three routes towards 1.140 are discussed within, with the most successful route involving a difluorocyclopropanation and radical induced ring-opening reaction as key steps. Once the desired building block was in hand, attempts at alkylating a nickel(II) alanine benzyl proline benzophenone (Ni-Ala-BPB) Schiff base complex were made. Efforts towards optimising this towards the preparation of 1.139 are described.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.804795  DOI: Not available
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