The design and synthesis of molecular tools for probing biological function

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2020
Thesis identifier
  • T15454
Person Identifier (Local)
  • 201573578
Qualification Level
Qualification Name
Department, School or Faculty
  • 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.
Advisor / supervisor
  • Jamieson, Craig
Resource Type
Date Created
  • 2019
Former identifier
  • 9912789093502996
Embargo Note
  • This thesis is restricted to Strathclyde users only until 1st April 2025.