Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

Research Article

Abstract

Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

Key words

bTSH Bovine thyroid stimulating hormone Oligosaccharides Glycan N-glycan Sulfonation Sulfation Metal cations Metal complexes ECD Electron capture Dissociation Fourier transform ion cyclotron resonance FT-ICR FTMS Tandem mass spectrometry Structural characterization IRMPD Infrared multiphoton dissociation 

Supplementary material

13361_2013_700_MOESM1_ESM.docx (205 kb)
ESM 1(DOCX 205 kb)

References

  1. 1.
    Bertozzi, C.R., Kiessling, L.L.: Chemical glycobiology. Science 291, 2357–2364 (2001)CrossRefGoogle Scholar
  2. 2.
    Rudd, P.M., Elliott, T., Cresswell, P., Wilson, I.A., Dwek, R.A.: Glycosylation and the Immune System. Science 291, 2370–2376 (2001)CrossRefGoogle Scholar
  3. 3.
    Ohtsubo, K., Marth, J.D.: Glycosylation in cellular mechanisms of health and disease. Cell 126, 855–867 (2006)CrossRefGoogle Scholar
  4. 4.
    Dube, D.H., Bertozzi, C.R.: Glycans in cancer and inflammation. Potential for therapeutics and diagnostics. Nat. Rev. Drug Disc. 4, 477–488 (2005)CrossRefGoogle Scholar
  5. 5.
    Lowe, J.B., Marth, J.D.: A genetic approach to mammalian glycan function. Annu. Rev. Biochem. 72, 643–691 (2003)CrossRefGoogle Scholar
  6. 6.
    Pilobello, K.T., Mahal, L.K.: Deciphering the glycocode: the complexity and analytical challenge of glycomics. Curr. Opin. Chem. Biol. 11, 300–305 (2007)CrossRefGoogle Scholar
  7. 7.
    Zhao, Y.Y., Takahashi, M., Gu, J.G., Miyoshi, E., Matsumoto, A., Kitazume, S., Taniguchi, N.: Functional roles of N-glycans in cell signaling and cell adhesion om cancer. Cancer Sci. 99, 1304–1310 (2008)CrossRefGoogle Scholar
  8. 8.
    Varki, A.: Biological roles of oligosaccharides—all of the theories are correct. Glycobiology 3, 97–130 (1993)CrossRefGoogle Scholar
  9. 9.
    Zaia, J.: Mass spectrometry of oligosaccharides. Mass Spectrom. Rev. 23, 161–227 (2004)CrossRefGoogle Scholar
  10. 10.
    Harvey, D.J.: Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates. Mass Spectrom. Rev. 18, 349–450 (1999)CrossRefGoogle Scholar
  11. 11.
    Mechref, Y., Novotny, M.V.: Structural investigations of glycoconjugates at high sensitivity. Chem. Rev. 102, 321–369 (2002)CrossRefGoogle Scholar
  12. 12.
    Marshall, A.G., Hendrickson, C.L., Jackson, G.S.: Fourier Transform ion cyclotron resonance mass spectrometry: a primer. Mass Spectrom. Rev. 17, 1–35 (1998)CrossRefGoogle Scholar
  13. 13.
    Marshall, A.G., Hendrickson, C.L.: High-resolution mass spectrometers. Annu. Rev. Anal. Chem. 1, 579–599 (2008)CrossRefGoogle Scholar
  14. 14.
    Park, Y.M., Lebrilla, C.B.: Application of Fourier transform ion cyclotron resonance mass spectrometry to oligosaccharides. Mass Spectrom. Rev. 24, 232–264 (2005)CrossRefGoogle Scholar
  15. 15.
    Zhou, W., Håkansson, K.: Structural determination of carbohydrates by fourier transform tandem mass spectrometry. Curr. Proteom. 8, 297–308 (2011)CrossRefGoogle Scholar
  16. 16.
    Zaia, J., McClellan, J.E., Costello, C.E.: Tandem mass spectrometric determination of the 4s/6s sulfation sequence in chondroitin sulfate oligosaccharides. Anal. Chem. 73, 6030–6039 (2001)CrossRefGoogle Scholar
  17. 17.
    Wheeler, S.F., Harvey, D.J.: Extension of the in-gel release method for structural analysis of neutral and sialylated n-linked glycans to the analysis of sulfated glycans: application to the glycans from bovine thyroid-stimulating hormone. Anal. Biochem. 296, 92–100 (2001)CrossRefGoogle Scholar
  18. 18.
    Zaia, J., Li, X.Q., Chan, S.Y., Costello, C.E.: Tandem mass spectrometric strategies for determination of sulfation positions and uronic acid epimerization in chondroitin sulfate oligosaccharides. J. Am. Soc. Mass Spectrom. 14, 1270–1281 (2003)CrossRefGoogle Scholar
  19. 19.
    Naggar, E.F., Costello, C.E., Zaia, J.: Competing fragmentation processes in tandem mass spectra of heparin-like glycosaminoglycans. J. Am. Soc. Mass Spectrom. 15, 1534–1544 (2004)CrossRefGoogle Scholar
  20. 20.
    Yu, G.L., Zhao, X., Yang, B., Ren, S.M., Guan, H.S., Zhang, Y.B., Lawson, A.M., Chai, W.G.: Sequence determination of sulfated carrageenan-derived oligosaccharides by high-sensitivity negative-ion electrospray tandem mass spectrometry. Anal. Chem. 78, 8499–8505 (2006)CrossRefGoogle Scholar
  21. 21.
    Desaire, H., Leary, J.A.: Detection and quantification of the sulfated disaccharides in chondroitin sulfate by electrospray tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 11, 916–920 (2000)CrossRefGoogle Scholar
  22. 22.
    Kailemia, M.J., Li, L.Y., Ly, M., Linhardt, R.J., Amster, I.J.: Complete mass spectral characterization of a synthetic ultralow-molecular-weight heparin using collision-induced dissociation. Anal. Chem. 84, 5475–5478 (2012)CrossRefGoogle Scholar
  23. 23.
    Domon, B., Costello, C.E.: A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj. J. 5, 397–409 (1988)CrossRefGoogle Scholar
  24. 24.
    Budnik, B.A., Haselmann, K.F., Zubarev, R.A.: Electron detachment dissociation of peptide di-anions: an electron–hole recombination phenomenon. Chem. Phys. Lett. 342, 299–302 (2001)CrossRefGoogle Scholar
  25. 25.
    Yang, J., Mo, J., Adamson, J.T., Håkansson, K.: Characterization of oligodeoxynucleotides by electron detachment dissociation Fourier transform ion cyclotron resonance mass spectrometry. Anal. Chem. 77, 1876–1882 (2005)CrossRefGoogle Scholar
  26. 26.
    Adamson, J.T., Håkansson, K.: Electron detachment dissociation of neutral and sialylated oligosaccharides. J. Am. Soc. Mass Spectrom. 18, 2162–2172 (2007)CrossRefGoogle Scholar
  27. 27.
    Huzarska, M., Ugalde, I., Kaplan, D.A., Hartmer, R., Easterling, M.L., Polfer, N.C.: Negative electron transfer dissociation of deprotonated phosphopeptide anions: choice of radical cation reagent and competition between electron and proton transfer. Anal. Chem. 82, 2873–2878 (2010)CrossRefGoogle Scholar
  28. 28.
    Zhang, J.H., Schubothe, K., Li, B.S., Russell, S., Lebrilla, C.B.: Infrared multiphoton dissociation of O-linked mucin-type oligosaccharides. Anal. Chem. 77, 208–214 (2005)CrossRefGoogle Scholar
  29. 29.
    Wolff, J.J., Chi, L., Linhardt, R.J., Amster, I.J.: Distinguishing glucuronic from iduronic acid in glycosaminoglycan tetrasaccharides by using electron detachment dissociation. Anal. Chem. 79, 2015–2022 (2007)CrossRefGoogle Scholar
  30. 30.
    Wolff, J.J., Laremore, T.N., Busch, A.M., Linhardt, R.J., Amster, I.J.: Electron detachment dissociation of dermatan sulfate oligosaccharides. J. Am. Soc. Mass Spectrom. 19, 294–304 (2008)CrossRefGoogle Scholar
  31. 31.
    Wolff, J.J., Laremore, T.N., Busch, A.M., Linhardt, R.J., Amster, I.J.: Influence of charge state and sodium cationization on the electron detachment dissociation and infrared multiphoton dissociation of glycosaminoglycan oligosaccharides. J. Am. Soc. Mass Spectrom. 19, 790–798 (2008)CrossRefGoogle Scholar
  32. 32.
    Wolff, J.J., Laremore, T.N., Leach, F.E., Linhardt, R.J., Amster, I.J.: Electron capture dissociation, electron detachment dissociation and infrared multiphoton dissociation of sucrose octasulfate. Eur. J. Mass Spectrom. 15, 275–281 (2009)CrossRefGoogle Scholar
  33. 33.
    Wolff, J.J., Amster, I.J., Chi, L., Linhardt, R.J.: Electron detachment dissociation of glycosaminoglycan tetrasaccharides. J. Am. Soc. Mass Spectrom. 18, 234–244 (2007)CrossRefGoogle Scholar
  34. 34.
    Wolff, J.J., Leach, F.E., Laremore, T.N., Kaplan, D.A., Easterling, M.L., Linhardt, R.J., Amster, I.J.: Negative electron transfer dissociation of glycosaminoglycans. Anal. Chem. 82, 3460–3466 (2010)CrossRefGoogle Scholar
  35. 35.
    Aguilan, J.T., Dayrit, F.M., Zhang, J.H., Ninonuevo, M.R., Lebrilla, C.B.: Structural Analysis of α-carrageenan sulfated oligosaccharides by positive mode Nano-ESI-FTICR-MS and MS/MS by SORI-CID. J. Am. Soc. Mass Spectrom. 17, 96–103 (2006)CrossRefGoogle Scholar
  36. 36.
    Liu, H., Håkansson, K.: Electron capture dissociation of tyrosine O-sulfated peptides complexed with divalent metal cations. Anal. Chem. 78, 7570–7576 (2006)CrossRefGoogle Scholar
  37. 37.
    Harvey, D.J.: Ionization and collision-induced fragmentation of N-linked and related carbohydrates using divalent cations. J. Am. Soc. Mass Spectrom. 12, 926–937 (2001)CrossRefGoogle Scholar
  38. 38.
    Cancilla, M.T., Wang, A.W., Voss, L.R., Lebrilla, C.B.: Fragmentation reactions in the mass spectrometry analysis of neutral oligosaccharides. Anal. Chem. 71, 3206–3218 (1999)CrossRefGoogle Scholar
  39. 39.
    Sible, E.M., Brimmer, S.P., Leary, J.A.: Interaction of first row transition metals with a1-2, a1-6 mannotriose and conserved trimannosyl core oligosaccharides: a comparative electrospray ionization study of doubly and singly charged complexes. J. Am. Soc. Mass Spectrom. 8, 32–42 (1997)CrossRefGoogle Scholar
  40. 40.
    König, S., Leary, J.A.: Evidence for linkage position determination in cobalt coordinated pentasaccharides using ion trap mass spectrometry. J. Am. Soc. Mass Spectrom. 9, 1125–1134 (1998)CrossRefGoogle Scholar
  41. 41.
    Hofmeister, G.E., Zhou, Z., Leary, J.A.: Linkage position determination in lithium-cationized disaccharides: tandem mass spectrometry and semi-empirical calculations. J. Am. Chem. Soc. 113, 5964–5970 (1991)CrossRefGoogle Scholar
  42. 42.
    Devakumar, A., Mechref, Y., Kang, P., Novotny, M.V., Reilly, J.P.: Identification of isomeric N-glycan structures by mass spectrometry with 157 nm laser-induced photofragmentation. J. Am. Soc. Mass Spectrom. 19, 1027–1040 (2008)CrossRefGoogle Scholar
  43. 43.
    Xie, Y.M., Lebrilla, C.B.: Infrared multiphoton dissociation of alkali metal-coordinated oligosaccharides. Anal. Chem. 75, 1590–1598 (2003)CrossRefGoogle Scholar
  44. 44.
    Lancaster, K.S., An, H.J., Li, B.S., Lebrilla, C.B.: Interrogation of N-linked oligosaccharides using infrared multiphoton dissociation in FT-ICR mass spectrometry. Anal. Chem. 78, 4990–4997 (2006)CrossRefGoogle Scholar
  45. 45.
    An, H.J., Miyamoto, S., Lancaster, K.S., Kirmiz, C., Li, B., Lam, K.S., Leiserowitz, G.S., Lebrilla, C.B.: Profiling of glycans in serum for the discovery of potential biomarkers for ovarian cancer. J. Proteome Res. 5, 1626–1635 (2006)CrossRefGoogle Scholar
  46. 46.
    Pikulski, M., Hargrove, A., Shabbir, S.H., Anslyn, E.V., Brodbelt, J.S.: Sequencing and characterization of oligosaccharides using infrared multiphoton dissociation and boronic acid derivatization in a quadrupole ion trap. J. Am. Soc. Mass Spectrom. 18, 2094–2106 (2007)CrossRefGoogle Scholar
  47. 47.
    Harvey, D.J., Naven, T.J.P., Kuster, B., Bateman, R.H., Green, M.R., Critchley, G.: Comparison of fragmentation modes for the structural determination of complex oligosaccharides ionized by matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun. Mass Spectrom. 9, 1556–1561 (1995)CrossRefGoogle Scholar
  48. 48.
    Harvey, D.J., Bateman, R.H., Green, B.N.: High-energy collision-induced fragmentation of complex oligosaccharides ionized by matrix-assisted laser desorption/ionization mass spectrometry. J. Mass Spectrom. 32, 167–187 (1997)CrossRefGoogle Scholar
  49. 49.
    Yu, S., Wu, S., Khoo, K.: Distinctive characteristics of MALDI-Q/TOF and TOF/TOF tandem mass spectrometry for sequencing of permethylated complex type N-glycans. Glycoconj. J. 23, 355–369 (2006)CrossRefGoogle Scholar
  50. 50.
    Devakumar, A., Thompson, M.S., Reilly, J.P.: Fragmentation of oligosaccharide ions with 157 nm vacuum ultraviolet light. Rapid Commun. Mass Spectrom. 19, 2313–2320 (2005)CrossRefGoogle Scholar
  51. 51.
    Devakumar, A., Mechref, Y., Kang, P., Novotny, M.V., Reilly, J.P.: Laser-induced photofragmentation of neutral and acidic glycans inside an ion-trap mass spectrometer. Rapid Commun. Mass Spectrom. 21, 1452–1460 (2007)CrossRefGoogle Scholar
  52. 52.
    McFarland, M.A., Marshall, A.G., Hendrickson, C.L., Nilsson, C.L., Fredman, P., Mansson, J.E.: Structural characterization of the GM1 ganglioside by infrared multiphoton dissociation/electron capture dissociation, and electron detachment dissociation electrospray ionization FT-ICR MS/MS. J. Am. Soc. Mass Spectrom. 16, 752–762 (2005)CrossRefGoogle Scholar
  53. 53.
    Budnik, B.A., Haselmann, K.F., Elkin, Y.N., Gorbach, V.I., Zubarev, R.A.: Applications of electron-ion dissociation reactions for analysis of polycationic chitooligosaccharides in Fourier Transform mass spectrometry. Anal. Chem. 75, 5994–6001 (2003)CrossRefGoogle Scholar
  54. 54.
    Adamson, J.T., Håkansson, K.: Electron capture dissociation of oligosaccharides ionized with alkali, alkaline earth, and transition metals. Anal. Chem. 79, 2901–2910 (2007)CrossRefGoogle Scholar
  55. 55.
    Zhao, C., Xie, B., Chan, S.Y., Costello, C.E., O'Connor, P.B.: Collisionally activated dissociation and electron capture dissociation provide complementary structural information for branched permethylated oligosaccharides. J. Am. Soc. Mass Spectrom. 19, 138–150 (2008)CrossRefGoogle Scholar
  56. 56.
    Liu, H.C., Håkansson, K.: Electron capture dissociation of divalent metal-adducted sulfated oligosaccharides. Int. J. Mass Spectrom. 305, 170–177 (2011)CrossRefGoogle Scholar
  57. 57.
    Tsybin, Y.O., Witt, M., Baykut, G., Kjeldsen, F., Håkansson, P.: Combined infrared multiphoton dissociation and electron capture dissociation with a hollow electron beam in Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun. Mass Spectrom. 17, 1759–1768 (2003)CrossRefGoogle Scholar
  58. 58.
    Caravatti, P., Allemann, M.: The infinity cell—a new trapped ion cell with radiofrequency covered trapping electrodes for Fourier transform ion cyclotron resonance mass spectrometry. Org. Mass Spectrom. 26, 514–518 (1991)CrossRefGoogle Scholar
  59. 59.
    Horn, D.M., Ge, Y., McLafferty, F.W.: Activated ion electron capture dissociation for mass spectral sequencing of larger (42 kDa) proteins. Anal. Chem. 72, 4778–4784 (2000)CrossRefGoogle Scholar
  60. 60.
    Senko, M.W., Canterbury, J.D., Guan, S., Marshall, A.G.: A high-performance modular data system for FT-ICR mass spectrometry. Rapid Commun. Mass Spectrom. 10, 1839–1844 (1996)CrossRefGoogle Scholar
  61. 61.
    Ledford Jr., E.B., Rempel, D.L., Gross, M.L.: Space Charge effects in fourier transform mass spectrometry mass calibration. Anal. Chem. 56, 2744–2748 (1984)CrossRefGoogle Scholar
  62. 62.
    Lohmann, K.K., von der Lieth, C.W.: GlycoFragment and GlycoSearchMS: Web tools to support the interpretation of mass spectra of complex carbohydrates. Nucleic Acids Res. 32, W261–W266 (2004)CrossRefGoogle Scholar
  63. 63.
    Green, E.D., Baenziger, J.U.: Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin. 1. Stuctural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones. J. Biol. Chem. 263, 25–35 (1988)Google Scholar
  64. 64.
    Håkansson, K., Cooper, H.J., Emmett, M.R., Costello, C.E., Marshall, A.G., Nilsson, C.L.: Electron capture dissociation and infrared multiphoton dissociation MS/MS of an N-glycosylated tryptic peptide yield complementary sequence information. Anal. Chem. 73, 4530–4536 (2001)CrossRefGoogle Scholar
  65. 65.
    Stensballe, A., Norregaard-Jensen, O., Olsen, J.V., Haselmann, K., Zubarev, R.A.: Electron capture dissociation of singly and multiply phosphorylated peptides. Rapid Commun. Mass Spectrom. 14, 1793–1800 (2000)CrossRefGoogle Scholar
  66. 66.
    Shi, S.D.-H., Hemling, M.E., Carr, S.A., Horn, D.M., Lindh, I., McLafferty, F.W.: Phosphopeptide/phosphoprotein mapping by electron capture dissociation mass spectrometry. Anal. Chem. 73, 19–22 (2001)CrossRefGoogle Scholar
  67. 67.
    Håkansson, K., Chalmers, M.J., Quinn, J.P., McFarland, M.A., Hendrickson, C.L., Marshall, A.G.: Combined electron capture and infrared multiphoton dissociation for multistage MS/MS in an FT-ICR mass spectrometer. Anal. Chem. 75, 3256–3262 (2003)CrossRefGoogle Scholar
  68. 68.
    Håkansson, K., Hudgins, R.R., Marshall, A.G., O'Hair, R.A.J.: Electron capture dissociation and infrared multiphoton dissociation of oligodeoxynucleotide dications. J. Am. Soc. Mass Spectrom. 14, 23–41 (2003)CrossRefGoogle Scholar
  69. 69.
    Yang, J., Håkansson, K.: Fragmentation of oligoribonucleotides from gas-phase ion-electron reactions. J. Am. Soc. Mass Spectrom. 17, 1369–1375 (2006)CrossRefGoogle Scholar
  70. 70.
    Ge, Y., Lawhorn, B.G., EINaggar, M., Strauss, E., Park, J.H., Begley, T.P., McLafferty, F.W.: Top down characterization of larger proteins (45 kDa) by electron capture dissociation mass spectrometry. J. Am. Chem. Soc. 124, 672–678 (2002)CrossRefGoogle Scholar
  71. 71.
    Penn, S.G., Cancilla, M.T., Lebrilla, C.B.: Collision-induced dissociation of branched oligosaccharide ions with analysis and calculation of relative dissociation thresholds. Anal. Chem. 68, 2331–2339 (1996)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2013

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of MichiganAnn ArborUSA
  2. 2.Baxter HealthcareThousand OaksUSA

Personalised recommendations