Fast fragmentation method for characterization of peptides with labile PTMs

DESCRIPTION (provided by applicant): Significant increase in the efficiency and speed of electron transfer dissociation (ETD) in tandem mass spectrometry (MS) will have a profound impact on its applications to the entire analytical field of characterization of posttranslational modifications (PTM) in proteins. At present, the applicability of ETD-based MS analysis as a unique analytical tool specifically targeting PTM is limited by its low speed and by inability of ETD to efficiently dissociate proteins orpeptides with low charge density. We plan to build a novel ETD ion source generating an energetic beam of negative ions to significantly improve efficiency and speed of PTM detection of both proteins and peptides. To demonstrate high rate of MS/MS analysisbased on ETD, we plan to utilize capabilities of house-built desktop FTMS instrument equipped with multi-electrode detection system, and record MS/MS mass spectra obtained from fast ETD process with high mass resolution and in a short time. PUBLIC HEALTH RELEVANCE: Utilizing complementary fragmentation methods is a broadly used approach in mass-spectrometry based analysis of complex protein mixtures providing reliable identification of posttranslation modifications in proteins. We plan to developa novel source providing fast fragmentation that will substantially improve and accelerate characterization of posttranslation modifications in proteins analyzed in tandem mass spectrometers. The source can be easily incorporated into a design of a varietyof tandem mass spectrometers. This will allow much better detection of disease-specific biomarkers from biological fluids or tissues.