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Title: A chemical alternative to phosphospecific antibodies
Author: Murray, James Ian
ISNI:       0000 0004 7963 6828
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Signal transduction cascades in living systems are commonly controlled via posttranslational phosphorylation and dephosphorylation of proteins. These processes are catalyzed and controlled in vivo by the action of kinase and phosphatase enzymes, which consequently play an important role in many disease states, including cancer and immune system disorders. Current techniques for phosphoproteome analysis (using isotopic labelling, chromatographic purification and phosphospecific antibodies) are undoubtedly very powerful, however, these approaches have yet to provide a generally applicable tool for phosphoproteome analysis despite the widespread utility such a technique would have. The use of small molecule organic catalysts capable of promoting selective phosphate esterification would provide an extremely useful alternative to these current techniques for use in, e.g. the labelling and pull-down of phosphorylated proteins. This thesis describes the development of aryl-N-oxide catalysts capable of promoting site selective phosphorylation of polyol and peptide derivatives. Whilst, ultimately, it was shown that these catalysts are not optimal for achieving selective phosphate esterification in biological systems, an alternate synthetic tool for phosphoproteomic analysis was developed. Progress in the development of this pyrophosphorylate, eliminate, tag (pPET) strategy and its current applications are discussed.
Supervisor: Spivey, Alan ; Woscholski, Rudiger Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral