Use this URL to cite or link to this record in EThOS:
Title: Peptidomimetic foldamers of β-secondary structural elements
Author: Ross, Jonathan E.
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Foldamers have the potential to be the synthetic equivalent of Nature's macromolecules; man-made oligomers that use a range of non-covalent interactions to fold into well defined structures. Chapter 1 introduces the challenges laid down by Gellman to chemists in creating foldamers; i) to design new polymers that reliably display interesting folding properties; ii) to be able to include novel and unnatural functional groups; and iii) make them easy to synthesise. Each of the foldamers made in this thesis will be evaluated against these challenges. Chapter 2 develops a mimic of the linear β-strand, based on alternating pyridyl/urea units, with the conformation enforced by dipolar repulsion. Conformational bias is demonstrated in the solution phase by computational and NMR studies, and in the solid phase by X-ray crystallography. The concept is extended to the inclusion of hydrophilic residues and conformation is maintained in a polar protic solvent. Chapter 3 describes the design and synthesis of a three- and four-stranded β-sheet mimic templated by the diphenylacetylene motif. The folding is enforced by a hydrogen bonding network demonstrated via extensive solution phase studies and X-ray crystallography. Chapter 4 explores the scope of this new architecture. The meander is successfully elongated to seven strands, and the structure shown to be amenable to the inclusion of D-amino acids and hydrophilic residues. The foldamer is therefore shown to meet all of Gellman's criteria. Chapter 5 uses the diphenylacetylene motif to study the factors involved in the formation of β-sheets, specifically the effect of side-chain identity on hydrogen bond strength. The difference in strengths is shown to be minimal, suggesting that β-sheet propensity is due to the energy changes in forming the extended conformation rather than forces between strands.
Supervisor: Hamilton, Andrew ; Thompson, Sam Sponsor: Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available