Ayogu, Jude Ikechukwu; (2024) Synthesis of fungal–D-luciferin chimera for bioluminescence. Doctoral thesis (Ph.D), UCL (University College London).

Text Ayogu_10189140_thesis.pdf Access restricted to UCL open access staff until 1 April 2025. Download (7MB)

Abstract

The generation and utilisation of luciferin analogues have garnered significant interest in bioluminescence imaging. However, enduring challenges exist due to the absorption and attenuation of light below 700 nm by tissues and blood, an issue that is particularly prevalent in deep-tissue imaging. This hindrance limits the effectiveness of D-luciferin in visualising intracellular processes. Past attempts to address this concern have centred on luciferase mutation, but unfortunately, these strategies are constrained by the inherent electronic properties of D-luciferin. Therefore, D-luciferin analogues, which are capable of emitting bioluminescence at longer wavelengths, are desirable. The possibility for electronic and structural modification of D-luciferin is nearly exhausted. This thesis examines an alternative approach: the synthesis of fungal-D-luciferin chimera for bioluminescence. While some existing D-luciferin analogues can emit up to 730-750 nm, their brightness is significantly reduced. This research investigates the potential for creating novel bioluminescent molecules from chimeric structures that merge known luciferins from two organisms. Two chimeras were synthesised, incorporating the light-activating component of fungal luciferin with the benzothiazole chromophore from D-luciferin. One chimera retained the 6-hydroxyl substituent in the D-luciferin, while the other featured a dimethyl amino group. Although amino luciferin does not occur naturally, it is a useful man-made compound. The first two were synthesised using methodology derived from existing literature and fungal luciferin synthesis. A third chimera was also synthesised, which inverts the initial design elements by combining the light-emitting portion from D-luciferin with the chromophore from fungal luciferin. All chimeras were completely characterised, and their fluorescence emission spectra were analysed under various solvent conditions. Bioluminescence evaluation of the chimera incorporating the 6-hydroxy and 6-dimethylamino-benzothiazoles exhibited bioluminescence emission at 630 and 600 nm, respectively. A preliminary synthesis of several additional fungal luciferin analogues was also undertaken. This study enhances the potential for more chimeric luciferin analogues to explore longer emission wavelengths and brighter emissions suitable for deeper bioluminescence imaging.

Download activity - last month

Export as CSVJSONXML

Download activity - last 12 months

Export as XMLJSONCSV

Downloads by country - last 12 months

Export as XMLJSONCSV

Archive Staff Only

View Item