Recent approaches to constraining peptide sequences into more structurally-defined α- helical secondary structures, so-called peptide stapling, are discussed. Stapled peptides are a class of therapeutics that have been shown to more effectively target protein-protein interactions, which are harder to target using a classical small-molecule therapeutic approach. Stapling a peptide constrains it into a well-defined secondary structure. This more accurately mimics the protein-protein interaction making the peptide a more viable therapeutic. Starting from the p53-MDM2 interaction, a protein-protein interaction with important implications in cell health, a known peptidyl inhibitor of this interaction was stapled and analysed for increased α-helicity. This was achieved by using monomers that utilise the copper (I) alkyne azide cycloaddition as a cross-linking methodology, which has been less well researched in the context of peptide stapling. The viability of a novel stapled peptomer inhibitor approach, accomplished using a new, optimised monomer synthesis, is investigated. Additionally, the synthesis of a ligand series designed for use in the copper(I) alkyne azide cycloaddition is also discussed.
Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:735679 |
Date | January 2016 |
Creators | Saunders, Alexander William |
Contributors | Hulme, Alison ; Bradley, Mark |
Publisher | University of Edinburgh |
Source Sets | Ethos UK |
Detected Language | English |
Type | Electronic Thesis or Dissertation |
Source | http://hdl.handle.net/1842/25664 |
Page generated in 0.0019 seconds