Electron capture dissociation (ECD) tandem mass spectrometry (MS/MS) is a powerful analytical tool for peptide and protein structure analysis. The product ion abundance (PIA) distribution in ECD MS/MS is known to vary as a function of electron irradiation period. This variation complicates the development of a method of peptide identification by correlation of ECD MS/MS data with experimental and theoretical mass spectra. Here, we first develop a kinetic model to describe primary electron capture by peptide dications leading to product ion formation and secondary electron capture resulting in product ion neutralization. We apply the developed kinetic model to calculate product ion formation rate constants and electron capture rate constants of product ions from ECD mass spectra acquired using various electron irradiation periods. Contrary to ECD PIA distributions, the product ion formation rate constants are shown to be independent of electron irradiation period and, thus, may be employed to characterize ECD product ion formation more universally. The electron capture rate constants of product ions in ECD Fourier transform ion cyclotron resonance MS were found to correlate (with a correlation factor, R2, of ca 0.9) with ion mobility cross sections of product ions in electron transfer dissociation. Finally, we demonstrate that the electron irradiation period influences the ratio of radical and even-electron c and z product ions.
ZubarevR.A.KelleherN.L.McLaffertyF.W., “Electron capture dissociation of multiply charged protein cations. A nonergodic process”, J. Am. Chem. Soc.120, 3265–3266 (1998). doi: http://dx.doi.org/10.1021/ja973478k
2.
ZubarevR.A.HornD.M.FridrikssonE.K.KelleherN.L.KrugerN.A.LewisM.A.CarpenterB.K.McLaffertyF.W., “Electron capture dissociation for structural characterization of multiply charged protein cations”, Anal. Chem.72, 563–573 (2000). doi: http://dx.doi.org/10.1021/ac990811p
3.
BakhtiarR.GuanZ., “Electron capture dissociation mass spectrometry in characterization of peptides and proteins”, Biotechnol. Lett.28, 1047–1059 (2006). doi: http://dx.doi.org/10.1007/s10529-006-9065-z
4.
SweetS.M.CooperH.J., “Electron capture dissociation in the analysis of protein phosphorylation”, Expert Rev. Proteomics4, 149–159 (2007). doi: http://dx.doi.org/10.1586/14789450.4.2.149
5.
ZhurovK.O.FornelliL.WodrichM.D.LaskayU.A.TsybinY.O., “Principles of electron capture and transfer dissociation mass spectrometry applied to peptide and protein structure analysis”, Chem. Soc. Rev.42, 5014–5030 (2013). doi: http://dx.doi.org/10.1039/C3CS35477F
6.
KonermannL.VahidiS.SowoleM.A., “Mass spectrometry methods for studying structure and dynamics of biological macromolecules”, Anal. Chem.86, 213–232 (2014). doi: http://dx.doi.org/10.1021/ac4039306
7.
LeveryS.B.SteentoftC.HalimA.NarimatsuY.ClausenH.VakhrushevS.Y., “Advances in mass spectrometry driven O-glycoproteomics”, Biochim. Biophys. Acta1850, 33–42 (2015). doi: http://dx.doi.org/10.1016/j.bbagen.2014.09.026
8.
ChanT.W.D.IpW.H.H., “Optimization of experimental parameters for electron capture dissociation of peptides in a Fourier transform mass spectrometer”, J. Am. Soc. Mass Spectrom.13, 1396–1406 (2002). doi: http://dx.doi.org/10.1016/S1044-0305(02)00703-1
9.
McFarlandM.A.ChalmersM.J.QuinnJ.P.HendricksonC.L.MarshallA.G., “Evaluation and optimization of electron capture dissociation efficiency in Fourier transform ion cyclotron resonance mass spectrometry”, J. Am. Soc. Mass Spectrom.16, 1060–1066 (2005). doi: http://dx.doi.org/10.1016/j.jasms.2005.03.020
10.
TsybinY.O.HendricksonC.L.BeuS.C.MarshallA.G., “Impact of ion magnetron motion on electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry”, Int. J. Mass Spectrom.255, 144–149 (2006). doi: http://dx.doi.org/10.1016/j.ijms.2005.11.014
11.
O'ConnorP.B.LinC.CournoyerJ. J.PittmanJ. L.BelyayevM.BudnikB. A., “Long-lived electron capture dissociation product ions experience radical migration via hydrogen abstraction”, J. Am. Soc. Mass Spectrom.17, 576–585 (2006). doi: http://dx.doi.org/10.1016/j.jasms.2005.12.015
12.
KjeldsenF.HaselmannK.F.BudnikB.A.JensenF.ZubarevR.A., “Dissociative capture of hot (3–13 eV) electrons by polypeptide polycations: An efficient process accompanied by secondary fragmentation”, Chem. Phys. Lett.356, 201–206 (2002). doi: http://dx.doi.org/10.1016/S0009-2614(02)00149-5
13.
MihalcaR.KleinnijenhuisA.McDonnellL.HeckA.R.HeerenR.A., “Electron capture dissociation at low temperatures reveals selective dissociations”, J. Am. Soc. Mass Spectrom.15, 1869–1873 (2004). doi: http://dx.doi.org/10.1016/j.jasms.2004.09.007
14.
PrellJ.S.O'BrienJ.T.HolmA.I.S.LeibR.D.DonaldW.A.WilliamsE.R., “Electron capture by a hydrated gaseous peptide: Effects of water on fragmentation and molecular survival”, J. Am. Chem. Soc.130, 12680–12689 (2008). doi: http://dx.doi.org/10.1021/ja8022434
15.
TsybinY.O.HeH.EmmettM.R.HendricksonC.L.MarshallA.G., “Ion activation in electron capture dissociation to distinguish between N-terminal and C-terminal product ions”, Anal. Chem.79, 7596–7602 (2007). doi: http://dx.doi.org/10.1021/ac071165u
16.
LinC.CournoyerJ.J.O'ConnorP.B., “Use of a double resonance electron capture dissociation experiment to probe fragment intermediate lifetimes”, J. Am. Soc. Mass Spectrom.17, 1605–1615 (2006). doi: http://dx.doi.org/10.1016/j.jasms.2006.07.007
17.
TurečekF.JulianR.R., “Peptide radicals and cation radicals in the gas phase”, Chem. Rev.113, 6691–6733 (2013). doi: http://dx.doi.org/10.1021/cr400043s
18.
LedvinaA.R.BeaucheneN.A.McAlisterG.C.SykaJ.E.P.SchwartzJ.C.Griep-RamingJ.WestphallM.S.CoonJ.J., “Activated-ion electron transfer dissociation improves the ability of electron transfer dissociation to identify peptides in a complex mixture”, Anal. Chem.82, 10068–10074 (2010). doi: http://dx.doi.org/10.1021/ac1020358
19.
Ben HamidaneH.VorobyevA.TsybinO.Y., “Repeatability and reproducibility of product ion abundances in electron capture dissociation mass spectrometry of peptides”, Eur. J. Mass Spectrom.17, 321–331 (2011). doi: http://dx.doi.org/10.1255/ejms.1143
20.
SchaubT.M.HendricksonC.L.HorningS.QuinnJ.P.SenkoM.W.MarshallA.G., “High-performance mass spectrometry: Fourier transform ion cyclotron resonance at 14.5 tesla”, Anal. Chem.80, 3985–3990 (2008). doi: http://dx.doi.org/10.1021/ac800386h
21.
TsybinY.O.HakanssonP.BudnikB.A.HaselmannK.F.KjeldsenF.GorshkovM.ZubarevR.A., “Improved low-energy electron injection systems for high rate electron capture dissociation in Fourier transform ion cyclotron resonance mass spectrometry”, Rapid Commun. Mass Spectrom.15, 1849–1854 (2001). doi: http://dx.doi.org/10.1002/rcm.448
22.
TsybinY.O.QuinnJ.P.TsybinO.Y.HendricksonC.L.MarshallA.G., “Electron capture dissociation implementation progress in Fourier transform ion cyclotron resonance mass spectrometry”, J. Am. Soc. Mass Spectrom.19, 762–771 (2008). doi: http://dx.doi.org/10.1016/j.jasms.2008.02.007
23.
BrownawellM.L.San FilippoJ., “Simulation of chemical instrumentation: II. A program for the synthesis of mass spectral isotopic abundances”, J. Chem. Educ.59, 663–665 (1982). doi: http://dx.doi.org/10.1021/ed059p663
LinC.CournoyerJ.J.O'ConnorP.B., “Probing the gas-phase folding kinetics of peptide ions by IR activated DR-ECD”, J. Am. Soc. Mass Spectrom.19, 780–789 (2008). doi: http://dx.doi.org/10.1016/j.jasms.2008.01.001
26.
TsybinY.O.WittM.BaykutG.HakanssonP., “Electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry in the electron energy range 0–50 eV”, Rapid Commun. Mass Spectrom.18, 1607–1613 (2004). doi: http://dx.doi.org/10.1002/rcm.1525
27.
BrownJ.PringleS.CampuzanoL.ChapmanR.HoyesJ., “Liquid chromatography–electron transfer dissociation–ion mobility on a quadrupole time of flight mass spectrometer”, Proceedings of the American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, Philadelphia, PA, 31 May–5 June 2009.
28.
Ben HamidaneH.ChiappeD.HartmerR.VorobyevA.MoniatteM.TsybinY.O., “Electron capture and transfer dissociation: Peptide structure analysis at different ion internal energy levels”, J. Am. Soc. Mass Spectrom.20, 567–575 (2009). doi: http://dx.doi.org/10.1016/j.jasms.2008.11.016
29.
Ben HamidaneH.HeH.TsybinO.Y.EmmettM.R.HendricksonC.L.MarshallA.G.TsybinY.O., “Periodic sequence distribution of product ion abundances in electron capture dissociation of amphipathic peptides and proteins”, J. Am. Soc. Mass Spectrom.20, 1182–1192 (2009). doi: http://dx.doi.org/10.1016/j.jasms.2009.02.015
30.
ZhangZ., “Prediction of electron-transfer/capture dissociation spectra of peptides”, Anal. Chem.82, 1990–2005 (2010). doi: http://dx.doi.org/10.1021/ac902733z
31.
KjeldsenF.ZubarevR., “Effects of peptide backbone amide-to-ester bond substitution on the cleavage frequency in electron capture dissociation and collision-activated dissociation”, J. Am. Soc. Mass Spectrom.22, 1441–1452 (2011). doi: http://dx.doi.org/10.1007/s13361-011-0151-7
32.
Ben HamidaneH.VorobyevA.LarregolaM.LukaszukA.TourwéD.LavielleS.KaroyanP.TsybinY.O., “Radical stability directs electron capture and transfer dissociation of β-amino acids in peptides”, Chem. Eur. J.16, 4612–4622 (2010). doi: http://dx.doi.org/10.1002/chem.200902480
33.
BabaT.HashimotoY.HasegawaH.HirabayashiA.WakiI., “Electron capture dissociation in a radio frequency ion trap”, Anal. Chem.76, 4263–4266 (2004). doi: http://dx.doi.org/10.1021/ac049309h
34.
SilivraO.KjeldsenF.IvoninI.ZubarevR., “Electron capture dissociation of polypeptides in a three-dimensional quadrupole ion trap: Implementation and first results”, J. Am. Soc. Mass Spectrom.16, 22–27 (2005). doi: http://dx.doi.org/10.1016/j.jasms.2004.09.015
