Electron-transfer dissociation tandem mass spectrometry

DESCRIPTION (provided by applicant): The purpose of this proposal is to deliver a new efficient method of ion fragmentation, namely electron-transfer dissociation (ETD), to any mass spectrometer including low- cost bench top instruments such as triple and single quadrupoles. Although most of modern mass spectrometers have tandem mass spectrometry (MS) capabilities using collision-activated dissociation (CAD), they can routinely handle only sequencing of peptides and small proteins (total length less than ~ 20 aminoacids). Unlike conventional CAD methods, the proposed ETD technique will be able to efficiently sequence large intact proteins. Also ETD can be used as an orthogonal (to standard CAD) fragmentation method resulting in an increase of the information content of tandem MS experiments. Since products of ETD retain mobile and labile groups such as phosphorylation and glycosylation, another specific benefit of the proposed technique is to provide a fast and easy way of determining the sites of post-translational modifications in proteins. The application of proteomics tools plays an important role in modern basic science, drug discovery and clinical applications. We propose a new technology for protein identification using tandem mass spectrometry, an essential strategy in proteomics today.