Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.818808
Title: A chemical investigation of mitochondrial protein modifications
Author: Norman, Abigail A. I.
ISNI:       0000 0004 9356 0903
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2020
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Abstract:
The work comprised in this thesis concerns the modification of mitochondrial proteins and can be split into two areas, the synthesis of tools to detect post-translational modifications and the development of methods to introduce modifications to mitochondrial proteins. Chapter 1 introduces the key concepts necessary to understand the nature and importance of the tools synthesised in the later chapters, including targeting small molecules to the mitochondria, the post-translational modifications of cysteine that are possible through the interaction with gaseous signalling molecules, and the reactivity of key metabolites with nucleophilic amino acid residues. Chapter 2 outlines a biochemical assay system used for the selective detection of protein persulfidation and the steps taken to optimise each chemical aspect of the assay. Additionally, novel mass spectrometric probes are described that utilise the specific reactivity of carbon iodine bonds, phosphines and isonitriles towards sulfur-based nucleophiles such as thiols or persulfides. Chapter 3 discusses published hydrogen sulfide and persulfide donors and then presents new mitochondria-targeted persulfide donors with differing modes of activation, which are the main focus of this thesis. Acylation of protein thiols by acyl-CoAs is another important post-translational modification. A probe for the mass spectrometric quantification of acyl-CoAs is described in chapter 4. Finally, chapter 5 details progress made towards delivering non-natural amino acids to mitochondria to be incorporated into newly synthesised proteins.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.818808  DOI: Not available
Keywords: QD Chemistry
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