H/D exchange of gas phase bradykinin ions in a linear quadrupole ion trap

Articles

Abstract

The gas phase H/D exchange reaction of bradykinin ions, as well as fragment ions of bradykinin generated through collisions in an orifice skimmer region, have been studied with a linear quadrupole ion trap (LIT) reflectron time-of-flight (rTOF) mass spectrometer system. The reaction in the trap takes only tens of seconds at a pressure of few mTorr of D2O or CD3OD. The exchange rate and hydrogen exchange level are not sensitive to the trapping q value over a broad range, provided q is not close to the stability boundary (q = 0.908). The relative rates and hydrogen exchange levels of protonated and sodiated +1 and +2 ions are similar to those observed previously by others with a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer system. The doubly and triply protonated ions show multimodal isotopic distributions, suggesting the presence of several different conformations. The y fragment ions show greater exchange rates and levels than a or b ions, and when water or ammonia is lost from the fragment ions, no exchange is observed.

Keywords

Exchange Rate Bradykinin Trapping Time Mass Spectrometer System Isotopic Envelope 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Hoaglund-Hyzer, C. S.; Counterman, A. E.; Clemmer, D. E. Anhydrous Protein Ions. Chem. Rev. 1999, 99, 3037–3079.CrossRefGoogle Scholar
  2. 2.
    Jarrold, M. F. Peptides and Proteins in the Vapor Phase. Ann. Rev. Phys. Chem. 2000, 51, 179–207.CrossRefGoogle Scholar
  3. 3.
    Campbell, S.; Rodgers, M. T.; Marzluff, E. M.; Beauchamp, J. L. Deuterium Exchange Reactions as a Probe of Biomolecule Structure. Fundamental Studies of Gas Phase H/D Exchange Reactions of Protonated Glycine Oligomers with D2O, CD3OD, CD3CO2D, and ND3. J. Am. Chem. Soc. 1995, 117, 12840–12854.CrossRefGoogle Scholar
  4. 4.
    Katta, V.; Chait, B. T. Conformational Changes in Proteins Probed by Hydrogen-Exchange Electrospray-Ionization Mass Spectrometry. Rapid Commun. Mass Spectrom. 1991, 5, 214–217.CrossRefGoogle Scholar
  5. 5.
    Eagen, J. R.; Smith, D. L. Investigating Protein Structure and Dynamics by Hydrogen Exchange MS. Anal. Chem. 2001, 73, 256A-265A.Google Scholar
  6. 6.
    Suckau, D.; Shi, Y.; Beu, S. C.; Senko, M. W.; Quinn, J. P.; Wampler, F. M. III; McLafferty, F. W. Coexisting Stable Conformations of Gaseous Protein Ions. Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 790–793.CrossRefGoogle Scholar
  7. 7.
    Wood, T. D.; Chorush, R. A.; Wampler, F. W. III; Little, D. P.; O’Conner, P. B.; McLafferty, F. W. Gas-Phase Folding and Unfolding of Cytochrome c Cations. Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 2451–2454.CrossRefGoogle Scholar
  8. 8.
    McLafferty, F. W.; Guan, Z.; Haupts, U.; Wood, T. D.; Kelleher, N. L. Gaseous Conformational Structures of Cytochrome c. J. Am. Chem. Soc. 1998, 120, 4732–4740.CrossRefGoogle Scholar
  9. 9.
    Freitas, M. A.; Hendrickson, C. L.; Emmett, M. R.; Marshall, A. G. High-Field Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Simultaneous Trapping and Gas Phase Hydrogen/Deuterium Exchange of Peptide Ions. J. Am. Soc. Mass Spectrom. 1998, 9, 1012–1019.CrossRefGoogle Scholar
  10. 10.
    Green, M. K.; Lebrilla, C. B. The Role of Proton-Bridged Intermediates in Promoting Hydrogen-Deuterium Exchange in Gas Phase Protonated Diamines, Peptides, and Proteins. Int. J. Mass Spectrom. Ion Proc. 1998, 175, 15–26.CrossRefGoogle Scholar
  11. 11.
    Freitas, M. A.; Marshall, A. G. Rate and Extent of Gas Phase Hydrogen/Deuterium Exchange of Bradykinins: Evidence for Peptide Zwitterions in the Gas Phase. Int. J. Mass Spectrom. 1999, 182/183, 221–231.CrossRefGoogle Scholar
  12. 12.
    Freitas, M. A.; Hendrickson, C. L.; Emmett, M. R.; Marshall, A. G. Gas-Phase Bovine Ubiquitin Cation Conformation Resolved by Gas-Phase Hydrogen/Deuterium Exchange Rate and Extent. Int. J. Mass Spectrom. 1999, 185/186/187, 565–575.Google Scholar
  13. 13.
    Green-Church, K. B.; Limbach, P. A.; Freitas, M. A.; Marshall, A. G. Gas-Phase Hydrogen/Deuterium Exchange of Positively Charged Mononucleotides by Use of Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2001, 12, 268–277.CrossRefGoogle Scholar
  14. 14.
    Solouki, T.; Fort, R. C. Jr.; Alomary, A.; Fattahi, A. Gas Phase Hydrogen Deuterium Exchange Reactions of a Model Peptide: FT-ICR and Computational Analyses of Metal Induced Conformational Mutations. J. Am. Soc. Mass Spectrom. 2001, 12, 1272–1285.CrossRefGoogle Scholar
  15. 15.
    Kaltashov, I. A.; Doroshenko, V. M.; Cotter, R. J. Gas Phase Hydrogen/Deuterium Exchange Reactions of Peptide Ions in a Quadrupole Ion Trap Mass Spectrometer. Proteins 1997, 28, 53–58.CrossRefGoogle Scholar
  16. 16.
    Reid, G. E.; O’Hair, R. A. J.; Styles, M. L.; McFadyen, W. D.; Simpson, R. J. Gas Phase Ion-Molecule Reactions in a Modified Ion Trap: H/D Exchange of Non-Covalent Complexes and Coordinatively Unsaturated Platinum Complexes. Rapid Commun. Mass Spectrom. 1998, 12, 1701–1708.CrossRefGoogle Scholar
  17. 17.
    Schaaff, T. G.; Stephenson, J. L. Jr.; McLuckey, S. A. The Reactivity of Gaseous Ions of Bradykinin and Its Analogues with Hydro- and Deuteroiodic Acid. J. Am. Chem. Soc. 1999, 121, 8907–8919.CrossRefGoogle Scholar
  18. 18.
    Schaaff, T. G.; Stephenson, J. L. Jr.; McLuckey, S. A. Gas Phase H/D Exchange Kinetics: DI versus D2O. J. Am. Soc. Mass Spectrom. 2000, 11, 167–171.CrossRefGoogle Scholar
  19. 19.
    Reyzer, M. L.; Brodbelt, J. S. Gas-Phase H/D Exchange Reactions of Polyamine Complexes: (M + H)+, (M + Alkali Metal+), and (M + 2H)2+. J. Am. Soc. Mass Spectrom. 2000, 11, 711–721.CrossRefGoogle Scholar
  20. 20.(a)
    Hofstadler, S. A.; Sannes-Lowery, K. A.; Griffey, R. H. Enhanced Gas-Phase Hydrogen-Deuterium Exchange of Oligonucleotide and Protein Ions Stored in an External Multipole Ion Reservoir. J. Mass Spectrom 2000, 35, 62–70.CrossRefGoogle Scholar
  21. 20.(b)
    Hofstadler, S. A.; Sannes-Lowery, K. A.; Griffey, R. H. A Gated-Beam Electrospray Ionization Source with an External Ion Reservoir. A New Tool for the Characterization of Biomolecules Using Electrospray Ionization Mass Spectrometry. Rapid. Commun. Mass Spectrom 1999, 13, 1971–1979.CrossRefGoogle Scholar
  22. 21.
    Witt, M.; Fuchser, J.; Baykut, G. In-Source H/D Exchange and Ion-Molecule Reactions Using Matrix Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry with Pulsed Collision and Reaction Gases. J. Am. Soc. Mass Spectrom. 2002, 13, 308–317.CrossRefGoogle Scholar
  23. 22.
    Gill, A. C.; Jennings, K. R.; Wyttenbach, T.; Bowers, M. T. Conformations of Biopolymers in the Gas Phase: A New Mass Spectrometric Method. Int. J. Mass Spectrom. 2000, 195/196, 685–697.CrossRefGoogle Scholar
  24. 23.
    Wyttenbach, T.; von Helden, G.; Bowers, M. T. Gas-Phase Conformation of Biological Molecules: Bradykinin. J. Am. Chem. Soc. 1996, 118, 8335–8364.CrossRefGoogle Scholar
  25. 24.
    Counterman, A. E.; Valentine, S. J.; Srebalus, C. A.; Henderson, S. C.; Hoaglund, C. S.; Clemmer, D. E. High-Order Structure and Dissociation of Gaseous Peptide Aggregates that are Hidden in Mass Spectra. J. Am. Soc. Mass Spectrom. 1998, 9, 743–759.CrossRefGoogle Scholar
  26. 25.
    Ling, Y.; Rodriquez, C. F.; Guo, Y.; Chu, I. K; Javahery, G.; Mak, W. A.; Hopkinson, A. C.; Siu, K. W. M. Structures and Energetics of Triply-Protonated Bradykinin. Proceedings of the 49th ASMS Conference on Mass Spectrometry and Allied Topics; Chicago, IL, May, 2001; WODam10:55Google Scholar
  27. 26.
    Schnier, P. D.; Price, W. D.; Jockusch, R. A.; Williams, E. R. Blackbody Infrared Radiative Dissociation of Bradykinin and Its Analogues: Energetics, Dynamics, and Evidence for Salt-Bridge Structures in the Gas Phase. J. Am. Chem. Soc. 1996, 118, 7178–7189.CrossRefGoogle Scholar
  28. 27.
    Price, W. D.; Schnier, P. D.; Williams, E. R. Tandem Mass Spectrometry of Large Biomolecule Ions by Blackbody Infrared Radiative Dissociation. Anal. Chem. 1996, 68, 859–866.CrossRefGoogle Scholar
  29. 28.
    Butcher, D. J.; Asano, K. G.; Goeringer, D. E.; McLuckey, S. A. Thermal Dissociation of Gaseous Bradykinin Ions. J. Phys. Chem. A 1999, 103, 8664–8671.CrossRefGoogle Scholar
  30. 29.
    Gimon-Kinsel, M. E.; Barbacci, D. C.; Russell, D. H. Conformations of Protonated Gas-Phase Bradykinin Ions: Evidence for Intramolecular Hydrogen Bonding. J. Mass Spectrom. 1999, 34, 124–136.CrossRefGoogle Scholar
  31. 30.
    Zhang, Z.; Li, W.; Guan, S.; Marshall, A. G. Higher-Order Structure of Gas-Phase Peptides from Gas-Phase H/D Exchange Experiments. Proceedings of the 44th ASMS Conference on Mass Spectrometry and Allied Topics; Portland, OR, 1996; p 1061Google Scholar
  32. 31.
    Wyttenbach, T.; Bowers, M. T. Gas Phase Conformations of Biological Molecules: The Hydrogen/Deuterium Exchange Mechanism. J. Am. Soc. Mass Spectrom. 1999, 10, 9–14.CrossRefGoogle Scholar
  33. 32.
    Levy-Seri, E.; Koster, G.; Kogan, A.; Gutman, K.; Reuben, B. G.; Lifshitz, C. An Electrospray Ionization-Flow Tube Study of H/D Exchange in Protonated Bradykinin. J. Phys. Chem. A 2001, 105, 5552–5559.CrossRefGoogle Scholar
  34. 33.
    Purves, R. W.; Barnett, D. A.; Ells, B.; Guevremont, R. Gas-Phase Conformers of the [M + 2H]2+ ion of Bradykinin Investigated by Combining High-Field Asymmetric Waveform Ion Mobility Spectrometry, Hydrogen/Deuterium Exchange, and Energy-Loss Measurements. Rapid Commun. Mass Spectrom. 2001, 15, 1453–1456.CrossRefGoogle Scholar
  35. 34.
    Campbell, J. M.; Collings, B. A.; Douglas, D. J. A New Linear Ion Trap Time-of-Flight System with Tandem Mass Spectrometry Capabilities. Rapid Commun. Mass Spectrom. 1998, 12, 1463–1474.CrossRefGoogle Scholar
  36. 35.
    Collings, B. A.; Campbell, J. M.; Mao, D.; Douglas, D. J. A Combined Linear Ion Trap Time-of-Flight System with Improved Performance and MSn Capabilities. Rapid Commun. Mass Spectrom. 2001, 15, 1777–1795.CrossRefGoogle Scholar
  37. 36.
    French, J. B. Molecular Beams for Rarefied Gasdynamic Research, North Atlantic Treaty Organization Advisory Group for Aerospace Research and Development. AGARDograph 112, p 22Google Scholar
  38. 37.
    Wagner, D. S.; Anderegg, R. J. Conformation of Cytochrome c Studied by Deuterium Exchange-Electrospray Ionization Mass Spectrometry. Anal. Chem. 1994, 66, 706–711.CrossRefGoogle Scholar
  39. 38.
    Miranker, A.; Robinson, C. V.; Radford, S. E.; Dobson, C. M. Investigation of Protein Folding by Mass Spectrometry. FASEB J 1996, 10, 93–101.Google Scholar
  40. 39.
    Eyles, S. J.; Dresch, T.; Gierasch, L. M.; Kaltashov, I. A. Unfolding Dynamics of a β-Sheet Protein Studied by Mass Spectrometry. J. Mass Spectrom. 1999, 34, 1289–1295.CrossRefGoogle Scholar
  41. 40.
    Babu, K. R.; Douglas, D. J. Methanol-Induced Conformations of Myoglobin at pH 4.0. Biochemistry 2000, 39, 14702–14710.CrossRefGoogle Scholar
  42. 41.
    Mao, D.; Ding, C.; Douglas, D. J. H/D Exchange of Myoglobin Ions in a Linear Quadrupole Ion Trap. Rapid Commun. Mass Spectrom. 2002, 16, 1941–1945.CrossRefGoogle Scholar
  43. 42.
    Schuler, K. E. Reaction Cross Sections, Rate Coefficients, and Nonequilibrium Kinetics. In Chemische Elementarprozesse; Heidberg, J.; Heydtmann, H.; Kohlmaier, G. H., Eds.; Springer-Velag: New York, 1968; p 1.Google Scholar
  44. 43.
    Asano, K. G.; Goeringer, D. E.; McLuckey, S. A. Thermal Dissociation in the Quadrupole Ion Trap: Ions Derived From Leucine Enkephalin. Int. J. Mass Spectrom. 1999, 185/186/187, 207–219.Google Scholar
  45. 44.
    Blatt, R.; Zoller, P.; Holzmüller, G.; Siemers, I. Brownian Motion of a Parametric Oscillator: A Model for Ion Confinement in Radio Frequency Traps. Z. Phys. DAt. Mol. Clusters 1986, 4, 121–126.CrossRefGoogle Scholar
  46. 45.
    Paradisi, C.; Todd, J. F. J.; Traldi, P.; Vettori, U. Boundary Effects and Collisional Activation in a Quadrupole Ion Trap. Org. Mass Spectrom. 1992, 27, 251–254.CrossRefGoogle Scholar
  47. 46.
    Paradisi, C.; Todd, J. F. J.; Vettori, U. Comparison of Collisional Activation by the “Boundary Effect” versus “Tickle” Excitation in an Ion Trap Mass Spectrometer. Org. Mass Spectrom. 1992, 27, 1210–1215.CrossRefGoogle Scholar
  48. 47.
    Curcuruto, O.; Fontana, S.; Traldi, P.; Celon, E. Effectiveness of the “Border Effect” for Daughter-Ion Spectrometer by Ion-Trap Mass Spectrometry. Rapid Commun. Mass Spectrom. 1992, 6, 322–323.CrossRefGoogle Scholar
  49. 48.
    Creaser, C. S.; O’Neill, K. E. Boundary-Effect Activated Dissociation in Ion Trap Tandem Mass Spectrometry. Org. Mass Spectrom. 1993, 28, 564–569.CrossRefGoogle Scholar
  50. 49.
    March, R. E.; Weir, M. R.; Londry, F. A.; Catinella, S.; Traldi, P.; Stone, J. A.; Jacobs, W. B. Controlled Variation of Boundary-Activated Ion Fragmentation Processes in a Quadrupole Ion Trap. Can. J. Chem. 1994, 72, 966–976.CrossRefGoogle Scholar
  51. 50.
    Vachet, R. W.; Glish, G. L. Boundary-Activated Dissociation of Peptide Ions in a Quadrupole Ion Trap. Anal. Chem. 1998, 70, 340–346.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2003

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of British ColumbiaVancouverCanada

Personalised recommendations