Abstract
The dissociation chemistry of primary fragment ions from the protonated proline-containing tripeptides glycylprolylglycine, prolylglycylglycine, and prolylprolylglycine was investigated by electrospray ionization multi-stage mass spectrometry. Calculations showed the a2 ions generated from b2 ions were cyclic, which is energetically more favorable than the linear form. The prolyl residue in the structure affected the energy hypersurface of the dissociation reaction from the b2 ion to the a2 ion. In the fragmentation of a2 ions, the iminium-imine complex corresponding to loss of CO from the a2 ion was suggested to be an ion-neutral complex (INC). The a1 ion was generated from direct separation of this INC, and the internal iminium ion, which was absent in PGG, was generated from another INC that was formed from the first INC via proton-bridged complex-mediated intramolecular proton transfer. Although these intermediates are unstable, their existence is supported by experiments and density functional theory calculations.
Article PDF
Similar content being viewed by others
References
Aebersold R, Goodlett D R. Mass spectrometry in proteomics. Chem Rev, 2001, 101: 269–295
Mann M, Hendrickson R C, Pandey A. Mass spectrometry-based proteomics. Nature, 2003, 422: 6928–6937
Savitski M M, Kjeldsen F, Nielsen M L, et al. Backbone carbonyl group basicities are related to gas-phase fragmentation of peptides and protein folding. Angew Chem Int Ed, 2007, 46: 1481–1484
Mueller M Q, Dreiocker F, Ihling C H, et al. Fragmentation behavior of a thiourea-based reagent for protein structure analysis by collision-induced dissociative chemical cross-linking. J Mass Spectrom, 2010, 45: 880–891
Fenn J B, Mann M, Meng C K, et al. Electrospray ionization for mass-spectrometry. Science, 1989, 246: 64–71
He W, Zheng O, Yu X. Fragmentation during nanoelectrospray ionization. Anal Chem, 2010, 82: 6534–6541
Chen S Y. Cloning and characterization of fragments related to proline synthesis and their effect on host cells. Chin Sci Bull, 1988, 33: 878
Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem, 1988, 60: 2299–2301
Chiappetta G, NDiaye S, Demey E, et al. Dansyl-peptides matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) and tandem mass spectrometric (MS/MS) features improve the liquid chromatography/MALDI-MS/MS analysis of the proteome. Rapid Commun Mass Spectrom, 2010, 24: 3021–3032
Rodriquez C F, Cunje A, Shoeib T, et al. Proton migration and tautomerism in protonated triglycine. J Am Chem Soc, 2001, 123: 3006–3012
Grewal R N, El Aribi H, Harrison A G, et al. Fragmentation of protonated tripeptides: The proline effect revisited. J Phys Chem B, 2004, 108: 4899–4908
Bythell B J, Csonka I P, Suhai S, et al. Gas-phase structure and fragmentation pathways of singly protonated peptides with N-terminal arginine. J Phys Chem B, 2010, 114: 15092–15105
Simon E S, Papoulias P G, Andrews P C. Gas-phase fragmentation characteristics of benzyl-aminated lysyl-containing tryptic peptides. J Am Soc Mass Spectrom, 2010, 21: 1624–1632
Sun F, Liu R, Zong W, et al. Unique approach to the mobile proton model: Influence of charge distribution on peptide fragmentation. J Phys Chem B, 2010, 114: 6350–6353
Bythell B J, Suhai S, Somogyi A, et al. Proton-driven amide bond-cleavage pathways of gas-phase peptide ions lacking mobile protons. J Am Chem Soc, 2009, 131: 14057–14065
Falick A M, Hines W M, Medzihradszky K F, et al. Low-mass ions produced from peptides by high-energy collision-induced dissociation in tandem mass spectrometry. J Am Soc Mass Spectrom, 1993, 4: 882–893
Papayannopoulos I A. The interpretation of collision-induced dissociation tandem mass spectra of peptides. Mass Spectrom Rev, 1995, 14: 49–73
Biemann K, Martin S. Mass spectrometric determination of the amino acid sequence of peptides and proteins. Mass Spectrom Rev, 1987, 6: 1–76
O’Hair R A J. The role of nucleophile-electrophile interactions in the unimolecular and bimolecular gas-phase ion chemistry of peptides and related systems. J Mass Spectrom, 2000, 35: 1377–1381
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
Polce M J, Ren D, Wesdemiotis C. Dissociation of the peptide bond in protonated peptides. J Mass Spectrom, 2000, 35: 1391–1398
Wysocki V H, Tsaprailis G, Smith L L, et al. Mobile and localized protons a framework for understanding peptide dissociation. J Mass Spectrom, 2000, 35: 1399–1406
Paizs B, Suhai S. Fragmentation pathways of protonated peptides. Mass Spectrom Rev, 2005, 24: 508–548
El Aribi H, Rodriquez C F, Almeida D R P, et al. Elucidation of fragmentation mechanisms of protonated peptide ions and their products: A case study on glycylglycylglycine using density functional theory and threshold collision-induced dissociation. J Am Chem Soc, 2003, 125: 9229–9236
El Aribi H, Orlova G, Rodriquez C F, et al. Fragmentation mechanisms of product ions from protonated tripeptides. J Phys Chem B, 2004, 108: 18743–18749
Verkerk U H, Siu C K, Steill J D, et al. a2 ion derived from triglycine: An N 1-protonated 4-imidazolidinone. J Phys Chem Lett, 2010, 1: 868–872
Morton T H. Gas phase analogues of solvolysis reactions. Tetrahedron, 1982, 38: 3195–3243
McAdoo D. Ion-neutral complexes in unimolecular decompositions. J Mass Spectrom Rev, 1988, 7: 363–393
Bowen R D. Ion-neutral complexes. Acc Chem Res, 1991, 24: 364–371
Morton T H. The reorientation criterion and positive ion-neutral complexes. Org Mass Spectrom, 1992, 27: 353–368
Longevialle P. Ion-neutral complexes in the unimolecular reactivity of organic cations in the gas phase. Mass Spectrom Rev, 1992, 11: 157–192
McAdoo D J, Morton T H. Gas-phase analogues of cage effects. Acc Chem Res, 1993, 26: 295–302
Liu P, Hu N, Pan Y, et al. Ion-neutral complexes resulting from dissociative protonation: Fragmentation of α-furanylmethyl benzyl ethers and 4-N,N-dimethylbenzyl benzyl ethers. J Am Soc Mass Spectrom, 2010, 21: 626–634
Tu Y P, He L, Fitch W, et al. Solvation in electrospray mass spectrometry: Effects on the reaction kinetics of fragmentation mediated by ion-neutral complexes. J Org Chem, 2005, 70: 5111–5118
Chai Y, Jiang K, Pan Y. Hydride transfer reactions via ion-neutral complex: Fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in mass spectrometry. J Mass Spectrom, 2010, 45: 496–503
Guo C, Wan J, Hu N, et al. An experimental and computational investigation on the fragmentation behavior of enaminones in electrospray ionization mass spectrometry. J Mass Spectrom, 2010, 45: 1291–1298
Hu N, Tu Y P, Jiang K, et al. Intramolecular charge transfer in the gas phase: Fragmentation of protonated sulfonamides in mass spectrometry. J Org Chem, 2010, 75: 4244–4250
Tu Y P, Huang Y, Atsriku C, et al. Intramolecular transacylation: Fragmentation of protonated molecules via ion-neutral complexes in mass spectrometry. Rapid Commun Mass Spectrom, 2009, 23: 1970–1976
Crestoni M E, Fornarini S, Lentini M, et al. Hydride-transfer reactions in the gas phase. 2. Anchimeric assistance in the H-transfer from 1,1-dimethylcyclopentane to alkyl cations. J Phys Chem, 1996, 100: 8285–8294
Harrison A G. Hydrogen interchange prior to the fragmentation of protonated molecules. Org Mass Spectrom, 1987, 22: 637–641
Tu Y P. Fragmentation of conjugated amides at the C-C(O) bond in electrospray mass spectrometry: A proton-bound dimeric intermediate identified by the kinetic method. Rapid Commun Mass Spectrom, 2004, 18: 1345–1351
Gitti R K, Lee B M, Walker J, et al. Structure of the amino-terminal core domain of the HIV-1 capsid protein. Science, 1996, 273: 231–235
Moriarty D F, Raleigh D P. Effects of sequential proline substitutions on amyloid formation by human amylin20–29. Biochemistry, 1999, 38: 1811–1818
Loo J A, Edmonds C G, Smith R D. Tandem mass spectrometry of very large molecules. 2. Dissociation of multiply charged proline-containing proteins from electrospray ionization. Anal Chem, 1993, 65: 425–438
Harrison A G. The gas-phase basicities and proton affinities of amino acids and peptides. Mass Spectrom Rev, 1997, 16: 201–217
Frisch M J, Trucks G W, Schlegel H B, et al. Gaussian 03. Revision B.01. Pittsburgh PA: Gaussian Inc., 2003
Dunbar R C, Hopkinson A C, Oomens J, et al. Conformation switching in gas-phase complexes of histidine with alkaline earth ions. J Phys Chem B, 2009, 113: 10403–10408
Siu C K, Guo Y, Saminathan I S, et al. Optimization of parameters used in algorithms of ion-mobility calculation for conformational analyses. J Phys Chem B, 2010, 114: 1204–1212
Ke Y, Zhao J, Verkerk U H, et al. Histidine, lysine, and arginine radical cations: Isomer control via the choice of auxiliary ligand (L) in the dissociation of [CuII(L)(amino acid)]·2+ complexes. J Phys Chem B, 2007, 111: 14318–14328
Siu C K, Ke Y, Orlova G, et al. Dissociation of the N-Cα bond and competitive formation of the [zn-H]·+ and [cn+2H]+ product ions in radical peptide ions containing tyrosine and tryptophan: The influence of proton affinities on product formation. J Am Soc Mass Spectrom, 2008, 19: 1799–1807
Paizs B, Szlavik Z, Lendvay G, et al. Formation of a +2 ions of protonated peptides. An ab initio study. Rapid Commun Mass Spectrom, 2000, 14: 746–755
Johnson R S, Martin S A, Bienmann K. Collision induced fragmentation of MH+ ions of peptides. Side chain specific fragmentation ions. Int J Mass Spectrom, 1988, 86: 137–154
McCormack A L, Somogyi A, Dongre A R, et al. Fragmentation of protonated peptides: Surface-induced dissociation in conjunction with a quantum mechanical approach. Anal Chem, 1993, 65: 2859–2872
Cox K A, Gaskell S J, Morris M, et al. 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
Rodriquez C F, Shoeib T, Chu I K, et al. Comparison between protonation, lithiation, and argentination of 5-oxazolones: A study of a key intermediate in gas-phase peptide sequencing. J Phys Chem A, 2000, 104: 5335–5342
Yalcin T, Khouw C, Csizmadia I G, et al. Why are B ions stable species in peptide spectra? J Am Soc Mass Spectrom, 1995, 6: 1165–1174
Yalcin T, Csizmadia I G, Peterson M R, et al. The structure and fragmentation of Bn (n>3) ions in peptide spectra. J Am Soc Mass Spectrom, 1996, 7: 233–242
Paizs B, Suhai S. Theoretical study of the main fragmentation pathways for protonated glycylglycine. Rapid Commun Mass Spectrom, 2001, 15: 651–663
Paizs B, Schnolzer M, Warnken U, et al. Cleavage of the amide bond of protonated dipeptides. Phys Chem Chem Phys, 2004, 6: 2691–2699
Harrison A G, Young A B, Schnoelzer M, et al. Formation of iminium ions by fragmentation of a2 ions. Rapid Commun Mass Spectrom, 2004, 18: 1635–1640
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at Springerlink.com
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
You, Z., Wen, Y., Jiang, K. et al. Fragmentation mechanism of product ions from protonated proline-containing tripeptides in electrospray ionization mass spectrometry. Chin. Sci. Bull. 57, 2051–2061 (2012). https://doi.org/10.1007/s11434-012-5117-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11434-012-5117-z