Electron-Transfer Dissociation Tandem Mass Spectrometry

DESCRIPTION (provided by applicant): The main goal of this proposal is to develop a novel MS interface device, capable to provide an efficient ECD/ETD-type fragmentation of peptide and proteins at any mass spectrometer including low-cost bench-top instrume nts such as single- and triple- quadrupoles. In this proposal we suggest using the novel hydroxyl radical induced dissociation (HRID) technique, developed in Phase I Studies, that offers various advantages, specific to ECD/ETD methods. The benefits of the HRID technology are clear and substantial. The HRID technique can be used as an orthogonal to standard CAD fragmentation method in order to minimize the probability of false positives which are considered as one of the serious problems in the bottom-up i dentification strategy. Importantly, the HRID technique is able to provide ECD/ETD-type tandem MS data even for singly charged peptides that will certainly be very attractive feature, for instance, for AP-MALDI users. We believe that the top-down approac h used with the HRID technique will provide the same key features as ECD and ETD methods, namely: (1) the efficient sequencing of large intact proteins and (2) the direct determination of the site of post-translational modifications in proteins. PUB LIC HEALTH RELEVANCE: 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 strateg y in proteomics today.