Photocages, photocaged nucleotides and subcellular delivery
Abstract: Photocages provide opportunities to activate a certain biological process, using light as an external trigger. The caged molecules are biologically inert, the activation of the substrates can be realized by irradiation. Thus, the release of the substrates can be manipulated with spatiotemporal control and in desired dosage. The main challenge photocages are facing is caused by UV-light activation. Conventional photocages are cleaved by UV light, but the irradiation with UV light can lead to cell damage, which limited their applications in living system. In addition, transmission of UV light through tissue is hampered by intense absorption and scattering of tissue components. Therefore, applications in tissue are tough to realize. One part of work in this thesis is to achieve photocages with longer wavelengths, ideally visible light absorption through modifications on coumarin scaffold. The strategies include extension of the π-conjugated system, thionation, and combination of these two methods.
Generally, the in vitro and in vivo investigations of phosphate containing small anionic molecules are restricted due to their cell impermeability. Some strategies were developed and applied to circumvent this issue, for example, masking the negative charges by biolabile or photolabile protecting groups, or using additional transporters. Solubility limitation, degradation of molecules, non-selective delivery, inability to penetrate tissue are commonly encountered disadvantages of the reported strategies. Second part of this thesis is to introduce potential transporters into the caged ATP (model molecule) covalently, to find a new strategy for intracellular delivery of phosphate containing small anionic molecules and realize the release of the molecule with spatial and temporal control. The covalent bond is built by click chemistry. The associated cellular uptake study and the localization of the molecules are investigated using a microscope. The quantification of the fluorescence generated by compounds that enter cells are evaluated by FACS. The tissue penetration ability of the synthesized molecules is examined using zebrafish embryos
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Universität Freiburg, Dissertation, 2023
- Keyword
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Fotochemische Reaktion
Nucleosid-Triphosphatase
Fotochemie
Cumarin
ATP
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2023
- Creator
- DOI
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10.6094/UNIFR/238833
- URN
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urn:nbn:de:bsz:25-freidok-2388339
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:46 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
Time of origin
- 2023
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Investigations on the synthesis and degradation of polyphosphate in vitro and its correlation to magic spot nucleotides
The 8th young faculty meeting – an active crowd attuned to modern challenges
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