Haris, Anisha (2022) Advanced applications of mass spectrometry for isomer differentiation and analysis of biomolecules. PhD thesis, University of Warwick.

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Abstract

The work presented herein focuses on the implementation of advanced fragmentation techniques with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to distinguish between isomeric species, including small metabolites and peptides. Applications of matrix-assisted laser desorption ionisation- time of flight mass spectrometry (MALDI-TOF MS) and FT-ICR MS for the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins are also investigated in this thesis.

The differentiation and relative quantification of isomeric species is of importance as the subtle changes in their physical structures may significantly impact their biological function. Current studies have demonstrated the potential of applying tandem mass spectrometry (MS/MS) techniques for direct isomer characterisation via generation of diagnostic fragment ions. Thus, the application of MS/MS methods has been explored in this thesis to characterize and relatively quantify the isomeric products of deamidation (chapter 2), modified tau and pi N-methylated actin peptides (chapter 3), and dihydroxylated vitamin D3 isomers (chapter 4).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus, responsible for causing coronavirus disease 2019 (COVID-19). In this work, MALDI-TOF MS was primarily used for the optimisation experiments to detect SARS-CoV-2 biomarker proteins including the nucleocapsid (N-protein) and the spike glycoprotein (S-protein). Focus was placed on various viral protein enrichment and extraction methods, which were applied to the standard SARS-CoV-2 proteins and then to COVID-19 negative and positive patient swab samples.

The final chapter of this thesis provides a conclusion on all the results presented herein and provides an outlook for future research. This can be used to further develop the current experimental work on the use of MS/MS techniques for the differentiation and relative quantification of various isomeric compounds as well the improvement of viral protein enrichment methods for MALDI-TOF MS analysis of SARS-CoV-2 biomarker proteins in complex patient samples.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QC Physics Q Science > QD Chemistry Q Science > QP Physiology R Medicine > RA Public aspects of medicine
Library of Congress Subject Headings (LCSH):	Mass spectrometry, Fourier transform spectroscopy, COVID-19 (Disease) -- Diagnosis, Isomerism, Biomolecules
Official Date:	January 2022
Dates:	Date Event January 2022 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	O’Connor, Peter B.
Format of File:	pdf
Extent:	xxxiv, 359 leaves : illustrations, charts
Language:	eng

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