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dc.contributor.advisorHulme, Alison
dc.contributor.advisorBradley, Mark
dc.contributor.authorSaunders, Alexander William
dc.date.accessioned2017-11-17T11:17:09Z
dc.date.available2017-11-17T11:17:09Z
dc.date.issued2016-11-29
dc.identifier.urihttp://hdl.handle.net/1842/25664
dc.description.abstractRecent 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.en
dc.contributor.sponsorEngineering and Physical Sciences Research Council (EPSRC)en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.subjectp53 proteinen
dc.subjectMDM2en
dc.subjectpeptidesen
dc.subjectpeptide staplingen
dc.subjectprotein-protein interactionen
dc.subjectstapled peptomer inhibitorsen
dc.titleNew approaches to stapled peptides targeting the p53-MDM2 interactionen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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