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Title: Development of chemical receptors and arrays for the identification of phosphatidylinositol phosphates and other phosphate related anions
Author: Behjat, Emma
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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This thesis concerns the synthesis and study of a series of metallo-receptors for the identification of phosphorylated species in an aqueous environment. Although the sensitive and selective detection of anions (such as phosphorylated species) has been extensively researched, it is still a challenging area within supramolecular chemistry. This is due to the anions' low charge-to-radius ratio, pH sensitivity and high hydrophilicity, which makes differentiation between anionic species problematic. The research presented in this thesis focuses on the development of a series of metal-based receptors for the use in Indicator Displacement Assays (IDAs), to effectively differentiate between phosphatidylinositol phosphates (PIPs) and other related anionic species. In the IDA, the receptors were bound to a range of colourimetric indicators and the addition of an anion induced a specific response that was recorded by UV-Vis spectroscopy. The UV-Vis response was used as a digital representation of the anion and was analysed with standard statistical methods, including principle component analysis and artificial neural networks. This analysis enabled the identification of various anions in both pure and complex solutions. Hierarchical cluster analysis (HCA) was also performed on the data, which allowed for an appreciation of the relationships present between the different anions. The binding affinities of the developed receptors were also investigated using the traditional dilution titrations and good affinities towards the phosphorylated species were obtained ranging from x103 - x109 Mol-1. In addition, the preferential binding of the receptors to different anions was evident, which justifies the success of the IDA. The interaction of the receptors with specific phosphatidylinositol phosphates was further investigated using phosphatase assays, the results from which demonstrates the ability of these receptors to interact with the different PIPs in vitro.
Supervisor: Vilar, Ramon; Woscholski, Rudiger Sponsor: Institute of Chemical Biology
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available