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Title: Development of an ion mobility mass spectrometer to study gas phase conformations of biomolecules
Author: McCullough, Bryan John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Design, development and implementation of a new Ion Mobility capable Mass Spectrometer – the MoQToF – are presented. The instrument is a Micromass Q-ToF modified to include a temperature regulated drift cell. Initial testing of the instrument to measure cross sections of well characterised proteins (cytochrome C, ubiquitin and lysozyme) in a range of charge states is described, showing the apparatus to perform well in comparison with values reported by others on analogous instruments. Ion mobility data is presented on a number of novel systems from small peptides to large proteins. The largest volume of work focuses on the study of β-defensins and related peptides. Β-defensins are small anti-microbial peptides that form a vital part of the innate immune system of all mammals, they are characterised by the presence of six conserved cysteine residues connected via disulphide bonds. Characterisation of these bonds (number and topology) using mass spectrometry based techniques is presented. The ion mobility data presented here probes the influence of these disulphide bonds on conformational flexibility. The mode of action of β-defensins is not known, two techniques designed to further understanding of this are described here.  Firstly, a mass spectrometry based technique in which the interaction between a defensin, DEFB107, and an artificial membrane is studied using hydrogen deuterium exchange revealing the N-terminal section of the peptide to interact favourably with the lipid bilayer. Secondly, a heparin binding assay is described revealing a relationship between heparin binding strength and anti-microbial activity. This interaction is further studied using the MoQToF and molecular modelling.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available