Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.581218
Title: Design and synthesis of inositol phosphate-based probes
Author: Slowey, Aine
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2013
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Abstract:
Inositol phosphates play a fundamental role in many intracellular processes. Of particular importance is the role of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] in the protein kinase B (PKB/Akt) signalling pathway. PtdIns(3,4,5)P3 recruits PKB to the cell membrane through binding interactions with its pleckstrin homology (PH) domain. In several human cancers, this signalling pathway is upregulated, resulting in increased cell growth and proliferation. In order to investigate the therapeutic potential of the PtdIns(3,4,5)P3–PH domain binding interaction, it is necessary to develop inositol phosphate-based probes. This DPhil dissertation highlights the synthesis of a number of derivatives of the PtdIns(3,4,5)P3 head group – inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. These derivatives incorporated phosphate isosteres at both the 3- and 5-positions of Ins(1,3,4,5)P4, through the utilisation of novel protection and deprotection strategies. In addition, this dissertation highlights the efficient synthesis of the natural product inositol 1,3-bisphosphate [Ins(1,3)P2] and our work towards the synthesis of inositol pyrophosphate derivatives.
Supervisor: Conway, Stuart Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.581218  DOI: Not available
Keywords: Organic chemistry ; Computational chemistry ; Chemical biology ; Chemistry & allied sciences ; Biomimetic synthesis ; Membrane proteins ; Natural products ; Synthetic organic chemistry ; Inositol ; Inositol Phosphate ; Inositol Pyrophosphate ; Protein Kinase B ; Organic Synthesis
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