Skip to main content

Generation and detection of multiply-charged peptides and proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) fourier transform ion cyclotron resonance mass spectrometry

Abstract

We report the coupling of a hybrid ionization source, matrix-assisted laser desorption electrospray ionization (MALDESI), to a Fourier transform-ion cyclotron resonance mass spectrometer (FT-ICR MS). The details of the source design and initial data are presented. Analysis of peptides and proteins ranging from 1 to 8.6 kDa resulted in high resolving power single-acquisition FT-ICR mass spectra with average charge-states highly correlated to those obtained by nanoESI, thus, providing strong evidence that the ESI process dictates the observed charge-state distribution. Importantly, unlike the recently introduced electrospray assisted laser desorption ionization (ELDI) source reported by Shiea and coworkers [1, 2], the data we have obtained to date rely on the use of an organic acid matrix. The results presented herein provide insight into the charging mechanism of this emerging ionization approach, while also expanding the utility of FT-ICR MS for top-down protein and complex mixture analysis.

References

  1. Huang, M. Z.; Hsu, H. J.; Lee, J. Y.; Jeng, J.; Shiea, J. Direct Protein Detection from Biological Media through Electrospray-Assisted Laser Desorption Ionization/Mass Spectrometry. J. Proteome Res. 2006, 5(5), 1107–1116.

    CAS  Article  Google Scholar 

  2. Shiea, J.; Huang, M. Z.; Hsu, H. J.; Lee, C. Y.; Yuan, C. H.; Beech, I.; Sunner, J. Electrospray-Assisted Laser Desorption/Ionization Mass Spectrometry for Direct Ambient Analysis of Solids. Rapid Commun. Mass Spectrom. 2005, 19(24), 3701–3704.

    CAS  Article  Google Scholar 

  3. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization for Mass-Spectrometry of Large Biomolecules. Science 1989, 246(4926), 64–71.

    CAS  Article  Google Scholar 

  4. Karas, M.; Hillenkamp, F. Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10,000 Daltons. Anal. Chem. 1988, 60(20), 2299–2301.

    CAS  Article  Google Scholar 

  5. Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. Protein and Polymer Analysis up to m/z 100,000 by Laser Ionization Time-of-Flight Mass Spectrometry. Rapid Commun. Mass Spectrom. 1988, 2(8), 151–153.

    CAS  Article  Google Scholar 

  6. Lee, C. C.; Chang, D. Y.; Jeng, J.; Shiea, J. Generating Multiply Charged Protein Ions Via Two-Step Electrospray Ionization Mass Spectrometry. J. Mass Spectrom. 2002, 37(1), 115–117.

    CAS  Article  Google Scholar 

  7. Coon, J. J.; Harrison, W. W. Laser Desorption-Atmospheric Pressure Chemical Ionization Mass Spectrometry for the Analysis of Peptides from Aqueous Solutions. Anal. Chem. 2002, 74(21), 5600–5605.

    CAS  Article  Google Scholar 

  8. Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization. Science 2004, 306(5695), 471–473.

    CAS  Article  Google Scholar 

  9. Cody, R. B.; Laramee, J. A.; Durst, H. D. Versatile New Ion Source for the Analysis of Materials in Open Air Under Ambient Conditions. Anal. Chem. 2005, 77(8), 2297–2302.

    CAS  Article  Google Scholar 

  10. McEwen, C. N.; McKay, R. G.; Larsen, B. S. Analysis of Solids, Liquids, and Biological Tissues Using Solids Probe Introduction at Atmospheric Pressure on Commercial LC/MS Instruments. Anal. Chem. 2005, 77(23), 7826–7831.

    CAS  Article  Google Scholar 

  11. Syka, J. E.; Marto, J. A.; Bai, D. L.; Horning, S.; Senko, M. W.; Schwartz, J. C.; Ueberheide, B.; Garcia, B.; Busby, S.; Muratore, T.; Shabanowitz, J.; Hunt, D. F. Novel Linear Quadrupole Ion Trap/FT Mass Spectrometer: Performance Characterization and Use in the Comparative Analysis of Histone H3 Posttranslational Modifications. J. Proteome Res. 2004, 3(3), 621–626.

    CAS  Article  Google Scholar 

  12. Henry, K. D.; Williams, E. R.; Wang, B. H.; McLafferty, F. W.; Shabanowitz, J.; Hunt, D. F. Fourier-Transform Mass Spectrometry of Large Molecules by Electrospray Ionization. Proc. Natl. Acad. Sci. U.S.A. 1989, 86(12), 9075–9078.

    CAS  Article  Google Scholar 

  13. Marshall, A. G.; Guan, S. H. Advantages of High Magnetic Field for Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Rapid Commun. Mass Spectrom. 1996, 10(14), 1819–1823.

    CAS  Article  Google Scholar 

  14. Nepomuceno, A. I.; Mason, C. J.; Muddiman, D. C.; Bergen, H. R., III; Zeldenrust, S. R. Detection of Genetic Variants of Transthyretin by Liquid Chromatography-Dual Electrospray Ionization Fourier-Transform Ion-Cyclotron-Resonance Mass Spectrometry. Clin. Chem. 2004, 50(9), 1535–1543.

    CAS  Article  Google Scholar 

  15. Kelleher, N. L. Top-Down Proteomics. Anal. Chem. 2004, 76(11), 197A-203A.

    Article  Google Scholar 

  16. Reid, G. E.; McLuckey, S. A. “Top Down” Protein Characterization Via Tandem Mass Spectrometry. J. Mass Spectrom. 2002, 37(7), 663–675.

    CAS  Article  Google Scholar 

  17. Bergen, H. R., III; Vasmatzis, G.; Cliby, W. A.; Johnson, K. L.; Oberg, A. L.; Muddiman, D. C. Discovery of Ovarian Cancer Biomarkers in Serum Using NanoLC Electrospray Ionization TOF and FT-ICR Mass Spectrometry. Dis. Markers 2003, 19(4/5), 239–249.

    CAS  Google Scholar 

  18. Johnson, K. L.; Mason, C. J.; Muddiman, D. C.; Eckel, J. E. Analysis of the Low Molecular Weight Fraction of Serum by LC-Dual ESI-FT-ICR Mass Spectrometry: Precision of Retention Time, Mass, and Ion Abundance. Anal. Chem. 2004, 76(17), 5097–5103.

    CAS  Article  Google Scholar 

  19. Senko, M. W.; Hendrickson, C. L.; Emmett, M. R.; Shi, S. D.-H.; Marshall, A. G. External Accumulation of Ions for Enhanced Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. J. Am. Soc. Mass Spectrom. 1997, 8, 970–976.

    CAS  Article  Google Scholar 

  20. Laiko, V. V.; Baldwin, M. A.; Burlingame, A. L. Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 2000, 72(4), 652–657.

    CAS  Article  Google Scholar 

  21. Hawkridge, A. M.; Zhou, L.; Lee, M. L.; Muddiman, D. C. Analytical Performance of a Venturi Device Integrated into an Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometer for Analysis of Nucleic Acids. Anal. Chem. 2004, 76(14), 4118–4122.

    CAS  Article  Google Scholar 

  22. Yang, P.; Cooks, R. G.; Ouyang, Z.; Hawkridge, A. M.; Muddiman, D. C. Gentle Protein Ionization Assisted by High-Velocity Gas Flow. Anal. Chem. 2005, 77(19), 6174–6183.

    CAS  Article  Google Scholar 

  23. Zhou, L.; Yue, B.; Dearden, D. V.; Lee, E. D.; Rockwood, A. L.; Lee, M. L. Incorporation of a Venturi Device in Electrospray Ionization. Anal. Chem. 2003, 75(21), 5978–5983.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David C. Muddiman.

Additional information

Published online September 6, 2006

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sampson, J.S., Hawkridge, A.M. & Muddiman, D.C. Generation and detection of multiply-charged peptides and proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) fourier transform ion cyclotron resonance mass spectrometry. The official journal of The American Society for Mass Spectrometry 17, 1712–1716 (2006). https://doi.org/10.1016/j.jasms.2006.08.003

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.jasms.2006.08.003