| Summary: | The following thesis details the structural and thermo-dynamic analysis of melittin, mutant tryptophan cage constructs and a series of truncated murine β-defensin 14 derivatives in solution, <i>in vacuo </i>and <i>in silico. </i>These experiments are used to identify correlations between their solvated and desolvated structural isoforms and, in doing so, investigate the role of mass spectrometry in the field of structural proteomics. The integrated experimental approach described in this thesis employs an array of analytical techniques including charge partition calculations, capillary-induced thermal degradation, gas phase hydrogen/deuterium exchange and collision induced dissociation to obtain a consensus view of the structural organisation of each analyte. Supporting evidence is presented from antimicrobial assays, molecular modelling and dynamics calculations, circular dichroism and fluorescence spectroscopy and ion mobility mass spectrometry. In addition, a novel gas inlet system is detailed which allows gas phase ion/molecule reactions, such as hydrogen/deuterium exchange, to be performed within the quadrupole ion traps of a Finnigan LCQ Classic. Significant differences are observed between the solvated and desolvated structures of most of the analyte ions examined, unless they exhibit a very stable structural fold. This suggests an important role for mass spectrometry in the field of structural proteomics, but, one that is limited to the comparative study of different solvation states, the analysis of biologically important membrane interactions and the analysis of peptides and proteins that are expressed or secreted into hydrophobic environments.
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