Lyu, Minyan;
(2024)
Design and synthesis of chimeric fungal luciferins.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Lyu_10183757_thesis.pdf Download (4MB) | Preview |
Abstract
Bioluminescence is a common light-emitting activity caused by a chemical reaction in nature performed by numerous species. The reaction is a low-toxicity bio-pathway in living cells and the cold light generated has a high signal-to-noise ratio. It is frequently used in medicinal imaging for studying cell activities in vitro and in vivo experiments. The most-widely applied bioluminescence is firefly bioluminescence, an oxidative reaction between firefly luciferase and firefly D-luciferin. Our group has worked on firefly bioluminescence for over a decade. We have focussed on improving red shifted bioluminescence wavelength and quantum yield via modification of the D-luciferin molecular structure. The thesis is based on expanding our studies in this area by exploring fungal bioluminescence. To explore new structures of bioluminescent molecules that may have superior qualities, different parts of D-luciferin and analogues were combined with different parts of fungal luciferin, to prepare chimeric fungal luciferin molecules. The research began with the simple modification of the electron-donating groups of fungal luciferin. We developed a highly efficient synthetic pathway towards 3-hydroxyhispidin derivatives. The electron donating part of D-luciferin, benzo[d]thiazol-6-ol, was introduced into the fungal luciferin molecule, making the first chimeric fungal luciferin. The sulphur heteroatom in benzo[d]thiazol-6-ol was substituted with nitrogen and oxygen, making 1H-benzo[d]imidazol-6-ol and benzo[d]oxazol-6-ol type chimeric fungal luciferins. The hydroxyl group on benzo[d]thiazol-6-ol was also substituted by an amino group, making 1H-benzo[d]imidazol-6-amine type chimeric fungal luciferin. The synthetic pathway towards the chimeric fungal luciferins was changed twice during the research to improve the overall yield and cis/trans ratio. The bioluminescence activity of these chimeric fungal luciferins will be tested by our collaborators in due course. Further beneficial modification of chimeric fungal luciferins can then be made based on the bioluminescence testing results to give new and improved luciferins for advanced imaging techniques.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Design and synthesis of chimeric fungal luciferins |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10183757 |
Archive Staff Only
 |
View Item |
