Gas-Phase Chemistry of Biological and Metal-Containing Ions

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Advances in proteomics have been made possible by conceptual developments and technological breakthroughs in biological mass spectrometry (MS). The long-term objective of our Discovery research program aims at elucidating the fundamental aspects of the science that underpins peptide and protein identification and characterization. The 20 essential amino-acid residues are not isomers and contain side-chain functional groups that influence peptide fragmentation chemistry. We are one of the very few leading groups internationally in this arena, in contrast to the very many groups specializing on applications. In the shorter term, and within the duration of the funding cycle to which this application applies, our objectives are to explore the structure, formation, energetics and fragmentation chemistry of (1) protonated peptides ([M + H]+); (2) molecular radical cations of peptides (M+); and (3) metallated peptide complexes. These are the classes of peptide ions encountered in protein/peptide identification and characterization. We will continue to advance our knowledge using a combination of experimental and theoretical approaches. Experimental techniques will include: tandem MS with isotopic labelling, where appropriate with 13C, 2H, 18O and 15N; and infrared multiple photon dissociation (IRMPD) spectroscopy through international collaboration. To augment structural and mechanistic determinations, theoretical calculations via principally density functional theory (DFT) will be employed. We will examine in detail the structures and chemistry of dehydrated protonated peptides. These products are nominal [bn]+ ions, a major fragment type that features prominently in automated peptide sequencing; however, these specific ions do not exhibit standard fragmentation chemistry and are, therefore, not utilized in standard proteomics algorithms. We will continue to advance our understanding of the fascinating structures and fragmentation chemistry of molecular radical cations of peptides, most of which have non-canonical structures that dissociate as driven by the charge or the radical. We will explore the effects of metal attachment, in particular that involving the lanthanides, on peptides. This is a new and unexplored field; preliminary results have shown a diversity of captivating and counterintuitive chemistries, resulting in high charge density and radical peptide product ions.**