Peptidomimetic foldamers of β-secondary structural elements
<p>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.</p> <p><b>Chapter 1</b> introduces the challenges laid down by Gellman...
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| Format: | Thesis |
| Language: | English |
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2016
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| _version_ | 1797086438901153792 |
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| author | Ross, J |
| author2 | Thompson, S |
| author_facet | Thompson, S Ross, J |
| author_sort | Ross, J |
| collection | OXFORD |
| description | <p>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.</p> <p><b>Chapter 1</b> 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.</p> <p><b>Chapter 2</b> 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.</p> <p><b>Chapter 3</b> 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 <em>via</em> extensive solution phase studies and X-ray crystallography.</p> <p><b>Chapter 4</b> 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.</p> <p><b>Chapter 5</b> 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. </p> |
| first_indexed | 2024-03-07T02:22:05Z |
| format | Thesis |
| id | oxford-uuid:a44b48d0-59fa-4f28-abac-7b66b6391d6c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:22:05Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | oxford-uuid:a44b48d0-59fa-4f28-abac-7b66b6391d6c2022-03-27T02:32:51ZPeptidomimetic foldamers of β-secondary structural elementsThesishttp://purl.org/coar/resource_type/c_db06uuid:a44b48d0-59fa-4f28-abac-7b66b6391d6cPeptidomimeticsOrganic ChemistryPeptidesEnglishORA Deposit2016Ross, JThompson, SSmith, MHamilton, A<p>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.</p> <p><b>Chapter 1</b> 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.</p> <p><b>Chapter 2</b> 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.</p> <p><b>Chapter 3</b> 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 <em>via</em> extensive solution phase studies and X-ray crystallography.</p> <p><b>Chapter 4</b> 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.</p> <p><b>Chapter 5</b> 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. </p> |
| spellingShingle | Peptidomimetics Organic Chemistry Peptides Ross, J Peptidomimetic foldamers of β-secondary structural elements |
| title | Peptidomimetic foldamers of β-secondary structural elements |
| title_full | Peptidomimetic foldamers of β-secondary structural elements |
| title_fullStr | Peptidomimetic foldamers of β-secondary structural elements |
| title_full_unstemmed | Peptidomimetic foldamers of β-secondary structural elements |
| title_short | Peptidomimetic foldamers of β-secondary structural elements |
| title_sort | peptidomimetic foldamers of β secondary structural elements |
| topic | Peptidomimetics Organic Chemistry Peptides |
| work_keys_str_mv | AT rossj peptidomimeticfoldamersofbsecondarystructuralelements |