Abstract
A novel mass spectrometric method has been developed for obtaining sequence information on small peptides. The peptides are desorbed as intact neutral molecules into a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR) by means of laser-induced acoustic desorption (LIAD). Reactions of the neutral peptides with the dimethoxyphosphenium ion, P(OCH3) +2 , occur predominantly by addition of the peptide to P(OCH3) +2 followed by the loss of two methanol molecules, thus yielding product ions with the composition (peptide+P−2H)+. Upon sustained off-resonance irradiation for collision-activated dissociation (SORI-CAD), the (peptide+P−2H)+ ions undergo successive losses of CO and NH=CHR or H2O, CO, and NH=CHR to yield sequence-related fragment ions in addition to the regular an- and bn-type ions. Under the same conditions, SORI-CAD of the analogous protonated peptides predominantly yields the regular an- and bn-type ions. The mechanisms of the reactions of peptides with P(OCH3) +2 and the dissociation of the (peptide+P−2H)+ ions were examined by using model peptides and molecular orbital calculations.
Article PDF
Similar content being viewed by others
References
Barber, M.; Bordoli, R. S.; Sedgwick, R. D.; Tyler, A. N. Fast Atom Bombardment of Solids (F.A.B.): A New Ion Source for Mass Spectrometry. J. Chem. Soc. Chem. Commun. 1981, 7, 325–327.
Beranová-Giorgianni, S.; Desiderio, D. M. Fast Atom Bombardment Mass Spectrometry of Synthetic Peptides. Methods Enzymol. 1987, 289, 478–499.
Caprioli, R. M. Bombardment Mass Spectrometry. Anal. Chem. 1990, 62, 477A-485A.
Karas, M.; Hillenkamp, F. Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10,000 Daltons. Anal. Chem. 1988, 60, 2299–2301.
Overberg, A.; Karas, M.; Hillenkamp, F.; Cotter, R. J. Matrix-assisted Laser Desorption of Large Biomolecules with a TEA-CO2-laser. Rapid Commun. Mass Spectrom. 1991, 5, 128–131.
Nordhoff, E.; Ingendoh, A.; Cramer, R.; Overberg, A.; Stahl, B.; Karas, M.; Hillenkamp, F.; Crain, P. F.; Chait, B. Matrix-assisted Laser Desorption/Ionization Mass Spectrometry of Nucleic Acids with Wavelengths in the Ultraviolet and Infrared. Rapid Commun. Mass Spectrom. 1992, 6, 771–776.
Yamashita, M.; Fenn, J. B. Electrospray Ion Source: Another Variation on the Free-jet Theme. J. Phys. Chem. 1984, 88, 4451–4459.
Yamashita, M.; Fenn, J. B. Negative Ion Production with the Electrospray Ion Source. J. Phys. Chem. 1984, 88, 4671–4675.
Wong, S. F.; Meng, C. K.; Fenn, J. B. Multiple Charging in Electrospray Ionization of Poly(ethylene glycols). J. Phys. Chem. 1988, 92, 546–550.
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, 64–71.
Smith, R. D.; Loo, J. A.; Edmonds, C. G.; Barinaga, C. J.; Udseth, H. R. New Developments in Biochemical Mass Spectrometry: Electrospray Ionization. Anal. Chem. 1990, 62, 882–899.
Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. Electrospray Ionization—Principles and Practice. Mass Spectrom. Rev. 1990, 9, 37–70.
Smith, R. D.; Loo, J. A.; Ogorzalek Loo, R. R.; Busman, M.; Udseth, H. R. Principles and Practice of Electrospray Ionization—Mass Spectrometry of Large Polypeptides and Proteins. Mass Spectrom. Rev. 1991, 10, 359–452.
Papayannopoulos, I. A. The Interpretation of Collision-induced Dissociation Tandem Mass Spectra of Peptides. Mass Spectrom. Rev. 1995, 14, 49–73.
Somogyi, A.; Wysocki, V. H.; Mayer, I. The Effect of Protonation Site on Bond Strengths in Simple Peptides: Application of Ab Initio and Modified Neglect of Differential Overlap Bond Orders and Modified Neglect of Differential Overlap Energy Partitioning. J. Am. Soc. Mass Spectrom. 1994, 5, 704–717.
Cox, K. A.; Gaskell, S. J.; Morris, M.; Whiting, A. Role of the Site of Protonation in the Low-energy Decompositions of Gas-phase Peptide Ions. J. Am. Soc. Mass Spectrom. 1996, 7, 522–531.
Gorman, G. S.; Amster, I. J. Photodissociation Studies of Small Peptide Ions by Fourier Transform Mass Spectrometry. Org. Mass Spectrom. 1993, 28, 437–444.
Dongré, A. R.; Somogyi, A.; Wysocki, V. H. Surface-induced Dissociation: An Effective Tool to Probe Structure, Energetics and Fragmentation Mechanisms of Protonated Peptides. J. Mass Spectrom. 1996, 31, 339–350.
Zubarev, R. A.; Kelleher, N. L.; McLafferty, F. W. Electron Capture Dissociation of Multiply Charged Protein Cations: A Nonergodic Process. J. Am. Chem. Soc. 1998, 120, 3265–3266.
Price, W. D.; Williams, E. R. Activation of Peptide Ions by Blackbody Radiation: Factors That Lead to Dissociation Kinetics in the Rapid Energy Exchange Limit. J. Phys. Chem. A. 1997, 101, 8844–8852.
Green, M. K.; Lebrilla, C. B. Ion-molecule Reactions as Probes of Gas-phase Structures of Peptides and Proteins. Mass Spectrom. Rev. 1997, 16, 53–71.
Freitas, M. A.; O’Hair, R. A. J.; Dua, S.; Bowie, J. H. The Methoxymethyl Cation Cleaves Peptide Bonds in the Gas Phase. Chem. Commun. 1997, 15, 1409–1410.
Yu, Y.-Q.; Stumpf, C. L.; Kenttämaa, H. I. Gas-phase Fragmentation of Di- and Tripeptides via Ion-molecule Reactions with ClPCl+. Int. J. Mass Spectrom. 2000, 195/196, 609–623.
Perez, J.; Petzold, C. J.; Watkins, M. A.; Vaughn, W. E.; Kenttämaa, H. I. Laser Desorption in Transmission Geometry Inside a Fourier-transform Ion Cyclotron Resonance Mass Spectrometer. J. Am. Soc. Mass Spectrom. 1999, 10, 1105–1110.
Perez, J.; Ramirez-Arizmendi, L. E.; Petzold, C. J.; Guler, L. P.; Nelson, E. D.; Kenttämaa, H. I. Laser-induced Acoustic Desorption/Chemical Ionization in Fourier-transform Ion Cyclotron Resonance Mass Spectrometry. Int. J. Mass Spectrom. 2000, 198, 173–188.
Petzold, C. J. Ph.D. Thesis, Purdue University, West Lafayette, IN, 2002.
Shea, R. C.; Habicht, S. C.; Vaughn, W. E.; Kenttämaa, H. I. Design and Characterization of a High-power Laser-induced Acoustic Desorption (LIAD) Probe Coupled with a Fourier-transform Ion Cyclotron Resonance Mass Spectrometer. In preparation.
Gauthier, J. W.; Trautman, T. R.; Jacbson, D. B. Sustained Off-resonance Irradiation for Collision-activated Dissociation Involving Fourier Transform Mass Spectrometry: Collision-activated Dissociation Technique That Emulates Infrared Multiphoton Dissociation. Anal. Chim. Acta. 1991, 246, 211–225.
Cowley, A. H.; Kemp, R. A. Synthesis and Reaction Chemistry of Stable Two-Coordinate Phosphorus Cations (Phosphenium Ions). Chem. Rev. 1985, 85, 367–382.
Redondo, P.; Largo, A.; Barrientos, C.; Ugalde, J. M. A Theoretical Study of the Structures and Stabilities of (H2PO)+ Species and the Proton Affinities of HPO and POH. J. Phys. Chem. 1991, 95, 4318–4323.
Harrison, J. F. Electronic Structure of the Phosphenium Ions PH2+, HPH+, and PF2+. J. Am. Chem. Soc. 1981, 103, 7406–7413.
Thoen, K. K.; Gao, L.; Ranatunga, T. D.; Vainiotalo, P.; Kenttämaa, H. I. Stereoselective Chemical Ionization Mass Spectrometry: Reactions of CH3OPOCH +3 with Cyclic Vicinal Diols. J. Org. Chem. 1997, 62, 8702–8707.
O’Hair, R. A. J. 1996, Gas-Phase Positive and Negative Ion Chemistry of Organophosphorus Compounds via Mass Spectrometric Techniques. Hartley, F. R., Ed.; In The Chemistry of Organophosphorus Compounds—Volume 4; pp 731–765. Wiley; New York, NY,
Thorne, L. R.; Anicich, V. G.; Huntress, W. T. An ICR Study of Ion-molecule Reactions of PH +n Ions. Chem. Phys. Lett. 1983, 98, 162–166.
Smith, D.; McIntosh, B. J.; Adams, N. G. A Selected Ion Flow Tube Study of the Reactions of the PH +n Ions (n=0 to 4) with Several Molecular Gases at 300 K. J. Chem. Phys. 1989, 90, 6213–6219.
Hodges, R. V.; McDonnell, T. J.; Beauchamp, J. L. Properties and Reactions of Trimethyl Phosphite, Trimethyl Phosphate, Triethyl Phosphate, and Trimethyl Phosphorothionate by Ion Cyclotron Resonance Spectroscopy. J. Am. Chem. Soc. 1980, 102, 1327–1332.
Holtz, D.; Beauchamp, J. L.; Eyler, J. R. Acidity, Basicity, and Ion-molecule Reactions of Phosphine in the Gas Phase by Ion Cyclotron Resonance Spectroscopy. J. Am. Chem. Soc. 1970, 92, 7045–7055.
Wanczek, K. P.; Hartmann, H.; Roeschenthaler, G. V. Ion Chemistry of Dimethylaminodifluorophosphine and Its Mixtures with Methyldifluorophosphine and Dimethylfluorophosphine, Investigated by Ion Cyclotron Resonance Spectrometry. Adv. Mass Spectrom. 1978, 7B, 1301–1307.
NcNeal, C. J.; Macfarlane, R. D.; Thurston, E. L. Thin Film Deposition by the Electrospray Method for Californium-252 Plasma Desorption Studies of Involatile Molecules. Anal. Chem. 1979, 51, 2036–2039.
Hensel, R. R.; King, R. C.; Ownes, K. G. Electrospray Sample Preparation for Improved Quantitation in Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry. Rapid Commun. Mass Spectrom. 1997, 11, 1785–1793.
Guan, S.; Kim, H. S.; Marshall, A. G.; Wahl, M. C.; Wood, T. D.; Xiang, X. Shrink-wrapping an Ion Cloud for High-performance Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Chem. Rev. 1994, 94, 2161–2182.
Dunbar, R. C. Infrared Radiative Cooling of Gas-phase Cooling of Ions. Mass Spectrom. Rev. 1992, 11, 309–339.
Chen, L.; Wang, T. C. L.; Ricca, T. L.; Marshall, A. G. Phase-modulated Stored Waveform Inverse Fourier Transform Excitation for Trapped Ion Mass Spectrometry. Anal. Chem. 1987, 59, 449–454.
Marshall, A. G.; Wang, T. C. L.; Ricca, T. L. Tailored Excitation for Fourier Transform Ion Cyclotron Mass Spectrometry. J. Am. Chem. Soc. 1985, 107, 7893–7897.
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Gaussian, Inc., Pittsburgh, PA, 1998.
Roepstorff, P.; Fohlman, J. Proposal for a Common Nomenclature for Sequence Ions in Mass Spectra of Peptide Ions. Biomed. Mass Spectrom. 1984, 11, 601.
Biemann, K. Contributions of Mass Spectrometry to Peptide and Protein Structure. Biomed. Environ. Mass Spectrom. 1988, 16, 99–111.
Nold, M. J.; Wesdemiotis, C.; Yalcin, T.; Harrison, A. G. Amide Bond Dissociation in Protonated Peptides: Structures of the N-terminal Ionic and Neutral Fragments. Int. J. Mass Spectrom. Ion Proc. 1997, 164, 137–153.
Cordero, M. M.; Houser, J. J.; Wesdemiotis, C. The Neutral Products Formed during Backbone Fragmentations of Protonated Peptides in Tandem Mass Spectrometry. Anal. Chem. 1993, 65, 1594–1601.
Yalcin, T.; Khouw, C.; Csizmadia, I. G.; Peterson, M. R.; Harrison, A. G. Why Are B Ions Stable Species in Peptide Spectra? J. Am. Soc. Mass Spectrom. 1995, 6, 1164–1174.
Arnott, D.; Kottmeier, D.; Yates, N.; Shabanowitz, J.; Hunt, D. F. Fragmentation of Multiply Protonated Peptides Under Low Energy Conditions. Proceedings of the 42nd ASMS Conference on Mass Spectrometry, Chicago, IL, 29 May–3 June 1994, p 470.
Ambihapathy, K.; Yalcin, T.; Leung, H.-W.; Harrison, A. G. Pathways to Immonium Ions in the Fragmentation of Protonated Peptides. J. Mass Spectrom. 1997, 32, 209–215.
Vachet, R. W.; Ray, K. L.; Glish, G. L. Origin of Product Ions in the MS/MS Spectra of Peptides in a Quadrupole Ion Trap. J. Am. Soc. Mass Spectrom. 1998, 9, 341–344.
Yalcin, T.; Csizmadia, I. G.; Peterson, M. R.; Harrison, A. G. The Structure and Fragmentation of Bn (n≥3) Ions in Peptide Spectra. J. Am. Soc. Mass Spectrom. 1996, 7, 233–242.
Vaisar, T.; Urban, J. Low-energy Collision Induced Dissociation of Protonated Peptides: Importance of an Oxazolone Formation for a Peptide Bond Cleavage. Eur. J. Mass Spectrom. 1998, 4, 359–364.
Schlosser, A.; Lehmann, W. D. Five-membered Ring Formation in Unimolecular Reactions of Peptides: A Key Structural Element Controlling Low-energy Collision-induced Dissociation of Peptides. J. Mass Spectrom. 2000, 35, 1382–1390.
Paizs, B.; Suhai, S. Towards Understanding the Tandem Mass Spectra of Protonated Oligopeptides. 1: Mechanism of Amide Bond Cleavage. J. Am. Soc. Mass Spectrom. 2004, 15, 103–113.
Polce, M. J.; Ren, D.; Wesdemiotis, C. Dissociation of the Peptide Bond in Protonated Peptides. J. Mass Spectrom. 2000, 35, 1391–1398.
Harrison, A. G. Fragmentation Reactions of Protonated Peptides Containing Phenylalanine: A Linear Free Energy Correlation in the Fragmentation of H-Gly-XXX-Phe-OH. Int. J. Mass Spec. 2002, 217, 185–193.
Grewal, R. N.; Aribi, H. E.; Harrison, A. G.; Michael Siu, K. W.; Hopkinson, A. C. Fragmentation of Protonated Tripeptides: The Proline Effect Revisited. J. Phys. Chem. B. 2004, 108, 4899–4908.
Laskin, J.; Denisov, E.; Futrell, J. H. Fragmentation of Small Peptides from Multiple-collision Activation and Surface-induced Dissociation in FT-ICR MS. Int. J. Mass Spectrom. 2002, 219, 189–201.
Aribi, H. E.; Orlova, G.; Rodriquez, C. F.; Almeida, D. R. P.; Hopkinson, A. C.; Siu, M. K. M. Fragmentation Mechanisms of Product Ions from Protonated Tripeptides. J. Phys. Chem. B. 2004, 108, 18743–18749.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published online December 6, 2006
Rights and permissions
About this article
Cite this article
Somuramasami, J., Kenttämaa, H.I. Evaluation of a novel approach for peptide sequencing: Laser-induced acoustic desorption combined with P(OCH3) +2 chemical ionization and collision-activated dissociation in a fourier transform ion cyclotron resonance mass spectrometer. J Am Soc Mass Spectrom 18, 525–540 (2007). https://doi.org/10.1016/j.jasms.2006.10.009
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.jasms.2006.10.009