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The Value of Activated Ion Electron Transfer Dissociation for High-Throughput Top-Down Characterization of Intact Proteins Nicholas M Riley, Jacek W. Sikora, Henrique S. Seckler, Joseph B. Greer, Ryan T. Fellers, Richard D. LeDuc, Michael S. Westphall, Paul M. Thomas, Neil L Kelleher, and Joshua J. Coon Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b01638 • Publication Date (Web): 20 Jun 2018 Downloaded from http://pubs.acs.org on June 22, 2018
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Analytical Chemistry
The Value of Activated Ion Electron Transfer Dissociation for High-Throughput Top-Down Characterization of Intact Proteins Nicholas M. Riley,1,2 Jacek W. Sikora,5 Henrique S. Seckler,5 Joseph B. Greer,5 Ryan T. Fellers,5 Richard D. LeDuc,5 Michael S. Westphall,1 Paul M. Thomas,5 Neil L. Kelleher,5 Joshua J. Coon1-4* 1
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Genome Center of Wisconsin, Departments of Chemistry and Biomolecular Chemistry, University of WisconsinMadison, Madison, WI, 53706, USA
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Morgridge Institute for Research, Madison, Wisconsin, 53706, USA
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National Resource for Translational and Developmental Proteomics, Departments of Chemistry and Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA *Corresponding author:
[email protected] ABSTRACT: High-throughput top-down proteomic experiments directly identify proteoforms in complex mixtures, making high quality tandem mass spectra necessary to deeply characterize proteins with many sources of variation. Collision-based dissociation methods offer expedient data acquisition, but often fail to extensively fragment proteoforms for thorough analysis. Electron-driven dissociation methods are a popular alternative approach, especially for precursor ions with high charge density. Combining infrared photo-activation concurrent with electron transfer dissociation (ETD) reactions, i.e., activated ion ETD (AI-ETD), can significantly improve ETD characterization of intact proteins, but benefits of AI-ETD have yet to be quantified in high-throughput top-down proteomics. Here we report the first application of AIETD to LC-MS/MS characterization of intact proteins (
