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Design, synthesis and application of novel light-activated molecular probes

Caged compounds are biologically active molecules that are rendered inert by masking an important functionality with a photolabile protecting, ‘caging’, group. The caging group can be removed by irradiation with light to reveal the active compound with restored pharmacological activity with high spatial and temporal control. This technology provides an ideal tool for the study of many chemical, physiological and biological systems. This DPhil dissertation highlights several projects in which caging technology has been employed to address biological problems and questions. The first example of spatially controlled mitochondrial inactivation is reported - a tool for the study of the role of mitochondria in Ca2+ signalling. Caged TRPV1 agonists and antagonists have been developed to probe TRPV1, specifically the location of the agonist-binding site. T cell activation has been controlled with light as a tool to gain insight into the adaptive immune response. Caged sodium channel blockers have been investigated. Wavelength-orthogonal photolysis in a neuronal system has been demonstrated using the neurotransmitters glutamate and GABA - this represents a significant advancement in caging technology. This dissertation also includes investigations into the development of novel caging groups.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:531792
Date January 2010
CreatorsStanton-Humphreys, Megan
ContributorsConway, Stuart
PublisherUniversity of Oxford
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://ora.ox.ac.uk/objects/uuid:1d0905c4-7fba-4796-92a5-848715204950

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