[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

Enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Glycomics has become an increasingly important field of research since glycans play critical roles in biology processes ranging from molecular recognition and signaling to cellular communication. Glycans often conjugate with other biomolecules, such as proteins and lipids, and alter their properties and functions, so glycan characterization is essential for understanding the effects they have on cellular systems. However, the analysis of glycans is extremely difficult due to their complexity and structural diversity (i.e., the number and identity of monomer units, and configuration of their glycosidic linkages and connectivities). In this work, we coupled ion mobility spectrometry with mass spectrometry (IMS-MS) to characterize glycan standards and biologically important isomers of synthetic αGal-containing O-glycans including glycotopes of the protozoan parasite Trypanosoma cruzi, which is the causative agent of Chagas disease. IMS-MS results showed significant differences for the glycan structural isomers when analyzed in positive and negative polarity and complexed with different metal cations. These results suggest that specific metal ions or ion polarities could be used to target and baseline separate glycan isomers of interest with IMS-MS.

Glycan isomers, such as fructose and glucose, show distinct separations in positive and negative ion mode

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bertozzi CR, Rabuka D, Varki A. Essentials of Glycobiology. 2009.

    Google Scholar 

  2. Raman R, Raguram S, Venkataraman G, Paulson JC, Sasisekharan R. Glycomics: an integrated systems approach to structure-function relationships of glycans. Nat Methods. 2005;2(11):817–24.

    Article  CAS  Google Scholar 

  3. Shriver Z, Raguram S, Sasisekharan R. Glycomics: a pathway to a class of new and improved therapeutics. Nat Rev Drug Discov. 2004;3(10):863–73.

    Article  CAS  Google Scholar 

  4. Kleene R, Schachner M. Glycans and neural cell interactions. Nat Rev Neurosci. 2004;5(3):195–208.

    Article  CAS  Google Scholar 

  5. Haltiwanger RS, Lowe JB. Role of glycosylation in development. Annu Rev Biochem. 2004;73(1):491–537.

    Article  CAS  Google Scholar 

  6. Spiro RG. Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology. 2002;12(4):43R–56.

    Article  CAS  Google Scholar 

  7. Varki A. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology. 1993;3(2):97–130.

    Article  CAS  Google Scholar 

  8. Molinari M. N-glycan structure dictates extension of protein folding or onset of disposal. Nat Chem Biol. 2007;3(6):313–20.

    Article  CAS  Google Scholar 

  9. Dwek, RA. Glycobiology: toward understanding the function of sugars. Chem Rev. 1996;96:683–720.

  10. Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126(5):855–67.

  11. Freeze HH. Genetic defects in the human glycome. Nat Rev Genet. 2006;7(7):537–51.

    Article  CAS  Google Scholar 

  12. Almeida IC, Ferguson MA, Schenkman S, Travassos LR. Lytic anti-α-galactosyl antibodies from patients with chronic Chagas’ disease recognize novel O-linked oligosaccharides on mucin-like glycosyl-phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi. Biochem J. 1994;304(3):793–802.

    Article  CAS  Google Scholar 

  13. Gazzinelli RT, Pereira ME, Romanha A, Gazzinelli G, Brener Z. Direct lysis of Trypanosoma cruzi: a novel effector mechanism of protection mediated by human anti-gal antibodies. Parasite Immunol. 1991;13(4):345–56.

    Article  CAS  Google Scholar 

  14. Almeida IC, Milani SR, Gorin PA, Travassos LR. Complement-mediated lysis of Trypanosoma cruzi trypomastigotes by human anti-alpha-galactosyl antibodies. J Immunol. 1991;146(7):2394–400.

    CAS  Google Scholar 

  15. Almeida IC, Krautz GM, Krettli AU, Travassos LR. Glycoconjugates of Trypanosoma cruzi: a 74 kD antigen of trypomastigotes specifically reacts with lytic anti-alpha-galactosyl antibodies from patients with chronic Chagas disease. J Clin Lab Anal. 1993;7:307–16.

    Article  CAS  Google Scholar 

  16. Milani SR, Travassos LR. Anti-alpha-galactosyl antibodies in chagasic patients. Possible biological significance. Braz J Med Biol Res. 1988;21(6):1275–86.

    CAS  Google Scholar 

  17. Boltje TJ, Buskas T, Boons G-J. Opportunities and challenges in synthetic oligosaccharide and glycoconjugate research. Nat Chem. 2009;1(8):611–22.

    Article  CAS  Google Scholar 

  18. Cummings Richard D, Pierce JM. The challenge and promise of glycomics. Chem Biol. 2014;21(1):1–15.

  19. Krasnova L, Wong C-H. Understanding the chemistry and biology of glycosylation with glycan synthesis. Annu Rev Biochem. 2016;85:599–630.

  20. Duus JO, Gotfredsen CH, Bock K. Carbohydrate structural determination by NMR spectroscopy: modern methods and limitations. Chem Rev. 2000;100:4589–614.

    Article  CAS  Google Scholar 

  21. Venetz D, Hess C, Lin C-w, Aebi M, Neri D. Glycosylation profiles determine extravasation and disease-targeting properties of armed antibodies. Proc Natl Acad Sci. 2015;112(7):2000–5.

    Article  CAS  Google Scholar 

  22. Dell A, Morris HR. Glycoprotein structure determination by mass spectrometry. Science. 2001;291:2351–6.

    Article  CAS  Google Scholar 

  23. Marino K, Bones J, Kattla JJ, Rudd PM. A systematic approach to protein glycosylation analysis: a path through the maze. Nat Chem Biol. 2010;6(10):713–23.

    Article  CAS  Google Scholar 

  24. Wyttenbach T, Bowers M. Gas-Phase Conformations: The Ion Mobility/Ion Chromatography Method. In: Schalley C, editor. Modern Mass Spectrometry. Topics in Current Chemistry: Springer Berlin Heidelberg; 2003. p. 207–32.

  25. Lanucara F, Holman SW, Gray CJ, Eyers CE. The power of ion mobility-mass spectrometry for structural characterization and the study of conformational dynamics. Nat Chem. 2014;6(4):281–94.

    Article  CAS  Google Scholar 

  26. Baker ES, Burnum-Johnson KE, Ibrahim YM, Orton DJ, Monroe ME, Kelly RT, et al. Enhancing bottom-up and top-down proteomic measurements with ion mobility separations. Proteomics. 2015;15(16):2766–76.

    Article  CAS  Google Scholar 

  27. Uetrecht C, Rose RJ, van Duijn E, Lorenzen K, Heck AJR. Ion mobility mass spectrometry of proteins and protein assemblies. Chem Soc Rev. 2010;39:1633–55.

    Article  CAS  Google Scholar 

  28. May JC, Goodwin CR, Lareau NM, Leaptrot KL, Morris CB, Kurulugama RT, et al. Conformational ordering of biomolecules in the gas phase: nitrogen collision cross sections measured on a prototype high resolution drift tube ion mobility-mass spectrometer. Anal Chem. 2014;86(4):2107–16.

    Article  CAS  Google Scholar 

  29. Gray CJ, Thomas B, Upton R, Migas LG, Eyers CE, Barran PE et al. Applications of ion mobility mass spectrometry for high throughput, high resolution glycan analysis. Biochimica et Biophysica Acta (BBA) - General Subjects. 2006;1860(8):1688-709.

  30. Zhu M, Bendiak B, Clowers B, Hill Jr HH. Ion mobility-mass spectrometry analysis of isomeric carbohydrate precursor ions. Anal Bioanal Chem. 2009;394:1853–67.

    Article  CAS  Google Scholar 

  31. Fenn LS, McLean JA. Structural resolution of carbohydrate positional and structural isomers based on gas-phase ion mobility-mass spectrometry. Phys Chem Chem Phys. 2011;13:2196–205.

    Article  CAS  Google Scholar 

  32. Both P, Green AP, Gray CJ, Šardzík R, Voglmeir J, Fontana C, et al. Discrimination of epimeric glycans and glycopeptides using IM-MS and its potential for carbohydrate sequencing. Nat Chem. 2014;6(1):65–74.

    Article  CAS  Google Scholar 

  33. Hofmann J, Hahm HS, Seeberger PH, Pagel K. Identification of carbohydrate anomers using ion mobility-mass spectrometry. Nature. 2015;526(7572):241–4.

    Article  CAS  Google Scholar 

  34. Pagel K, Harvey DJ. Ion mobility-mass spectrometry of complex carbohydrates: collision cross sections of sodiated N-linked glycans. Anal Chem. 2013;85(10):5138–45. doi:10.1021/ac400403d.

    Article  CAS  Google Scholar 

  35. Huang Y, Dodds ED. Discrimination of isomeric carbohydrates as the electron transfer products of Group II Cation Adducts by ion mobility spectrometry and tandem mass spectrometry. Anal Chem. 2015;87(11):5664–8.

    Article  CAS  Google Scholar 

  36. Ashmus RA, Schocker NS, Cordero-Mendoza Y, Marques AF, Monroy EY, Pardo A, et al. Potential use of synthetic [small alpha]-galactosyl-containing glycotopes of the parasite Trypanosoma cruzi as diagnostic antigens for Chagas disease. Org Biomol Chem. 2013;11(34):5579–83.

    Article  CAS  Google Scholar 

  37. Schocker NS, Portillo S, Brito CRN, Marques AF, Almeida IC, Michael K. Synthesis of Galα(1,3)Galβ(1,4)GlcNAcα-, Galβ(1,4)GlcNAcα- and GlcNAc-containing neoglycoproteins and their immunological evaluation in the context of Chagas disease. Glycobiology. 2016;26(1):39–50.

    CAS  Google Scholar 

  38. Tang K, Shvartsburg AA, Lee H-N, Prior DC, Buschbach MA, Li F, et al. High-sensitivity ion mobility spectrometry/mass spectrometry using electrodynamic ion funnel interfaces. Anal Chem. 2005;77(10):3330–9.

    Article  CAS  Google Scholar 

  39. Ibrahim Y, Tang K, Tolmachev AV, Shvartsburg AA, Smith RD. Improving mass spectrometer sensitivity using a high-pressure electrodynamic ion funnel interface. J Am Soc Mass Spectrom. 2006;17(9):1299–305.

  40. Belov ME, Clowers BH, Prior DC, Danielson Iii WF, Liyu AV, Petritis BO, et al. Dynamically multiplexed ion mobility time-of-flight mass spectrometry. Anal Chem. 2008;80(15):5873–83.

    Article  CAS  Google Scholar 

  41. Clowers BH, Ibrahim YM, Prior DC, Danielson WF, Belov ME, Smith RD. Enhanced ion utilization efficiency using an electrodynamic ion funnel trap as an injection mechanism for ion mobility spectrometry. Anal Chem. 2008;80(3):612–23.

    Article  CAS  Google Scholar 

  42. Pence HE, Williams A. ChemSpider: an online chemical information resource. J Chem Educ. 2010;87(11):1123–4.

    Article  CAS  Google Scholar 

  43. Csizmadia JSaF, editor. A method for calculating the pKa values of small and large molecules. American Chemical Society Spring meeting; March 25-29th, 2007.

  44. Halgren TA. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem. 1996;17(5–6):490–519.

    Article  CAS  Google Scholar 

  45. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform. 2012;4(1):1–17.

    Article  Google Scholar 

  46. Valiev M, Bylaska EJ, Govind N, Kowalski K, Straatsma TP, Van Dam HJJ, et al. NWChem: a comprehensive and scalable open-source solution for large scale molecular simulations. Comput Phys Commun. 2010;181(9):1477–89.

  47. Becke AD. Density‐functional thermochemistry. III. The role of exact exchange. J Chem Phys. 1993;98(7):5648–52.

  48. Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B. 1988;37(2):785–9.

    Article  CAS  Google Scholar 

  49. Vosko SH, Wilk L, Nusair M. Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can J Phys. 1980;58(8):1200–11.

    Article  CAS  Google Scholar 

  50. Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J Phys Chem. 1994;98(45):11623–7.

    Article  CAS  Google Scholar 

  51. Francl MM, Pietro WJ, Hehre WJ, Binkley JS, Gordon MS, DeFrees DJ, et al. Self‐consistent molecular orbital methods. XXIII. A polarization‐type basis set for second‐row elements. J Chem Phys. 1982;77(7):3654–65.

  52. Hariharan PC, Pople JA. The influence of polarization functions on molecular orbital hydrogenation energies. Theor Chim Acta. 1973;28(3):213–22.

    Article  CAS  Google Scholar 

  53. Rassolov VA, Ratner MA, Pople JA, Redfern PC, Curtiss LA. 6-31G* basis set for third-row atoms. J Comput Chem. 2001;22(9):976–84.

    Article  CAS  Google Scholar 

  54. Marklund Erik G, Degiacomi Matteo T, Robinson Carol V, Baldwin Andrew J, Benesch Justin LP. Collision cross sections for structural proteomics. Structure. 2015;23(4):791–9.

  55. Feinman RD, Fine EJ. Fructose in perspective. Nutr Metab. 2013;10(1):1–12.

    Article  Google Scholar 

  56. Huang Y, Dodds ED. Ion mobility studies of carbohydrates as group I adducts: isomer specific collisional cross section dependence on metal ion radius. Anal Chem. 2013;85(20):9728–35.

    Article  CAS  Google Scholar 

  57. Huang Y, Dodds ED. Ion-neutral collisional cross sections of carbohydrate isomers as divalent cation adducts and their electron transfer products. Analyst. 2015;140(20):6912–21.

    Article  CAS  Google Scholar 

  58. Gaye MM, Nagy G, Clemmer DE, Pohl NLB. Multidimensional analysis of 16 glucose isomers by ion mobility spectrometry. Anal Chem. 2016;88(4):2335–44.

    Article  CAS  Google Scholar 

  59. Avila JL, Rojas M, Galili U. Immunogenic Gal alpha 1–3Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania. J Immunol. 1989;142(8):2828–34.

    CAS  Google Scholar 

  60. Soares RP, Torrecilhas AC, Assis RR, Rocha MN, Castro FAM, Freitas GF, et al. Intraspecies variation in Trypanosoma cruzi GPI-mucins: biological activities and differential expression of α-galactosyl residues. Am J Trop Med Hyg. 2012;87(1):87–96.

    Article  CAS  Google Scholar 

  61. Izquierdo L, Marques AF, Gallego M, Sanz S, Tebar S, Riera C, et al. Evaluation of a chemiluminescent enzyme-linked immunosorbent assay for the diagnosis of Trypanosoma cruzi infection in a nonendemic setting. Mem Inst Oswaldo Cruz. 2013;108:928–31.

    Article  Google Scholar 

  62. Buscaglia CA, Campo VA, Frasch ACC, Di Noia JM. Trypanosoma cruzi surface mucins: host-dependent coat diversity. Nat Rev Microbiol. 2006;4(3):229–36.

    Article  CAS  Google Scholar 

  63. Deng L, Ibrahim YM, Baker ES, Aly NA, Hamid, AM, Zhang X, et al. Ion mobility separations of isomers based upon long path length structures for lossless ion manipulations combined with mass spectrometry. ChemistrySelect. 2016;1(10):2396–9.

Download references

Acknowledgments

Portions of this research were supported by grants from the National Institute of Environmental Health Sciences of the NIH (R01ES022190) (ESB), NIH grant R21CA199744 (KT), NIH grants R21AI079618 and R21AI115451 (ICA and KM), Robert J. Kleberg Jr. and Helen C. Kleberg Foundation grant (ICA and KM), Bridges to the Doctorate scholarship (NSF grants HRD-1139929) (NSS), Biomolecule Analysis Core Facility at UTEP, NIHMD grant G12MD007592, National Institute of General Medical Sciences grants P41 GM103493 (RDS) and P41 GM104603 (CEC), the Laboratory Directed Research and Development Program, and the Microbes in Transition (MinT) Initiative at Pacific Northwest National Laboratory. This research utilized capabilities developed by the Pan-omics program (funded by the U.S. Department of Energy Office of Biological and Environmental Research Genome Sciences Program). This work was performed in the W. R. Wiley Environmental Molecular Sciences Laboratory (EMSL), a DOE national scientific user facility at the Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle for the DOE under contract DE-AC05-76RL01830.

Author information

Author notes

    Authors and Affiliations

    1. Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, 902 Battelle Blvd, P.O. Box 999, MSIN K8-98, Richland, WA, 99352, USA

      Xueyun Zheng, Ryan S. Renslow, Daniel J. Orton, Keqi Tang, Richard D. Smith & Erin S. Baker

    2. Skaggs School of Pharmacy and Pharmaceutical Sciences, Anschutz Medical Campus, University of Colorado, 1380 Lawrence Street, Denver, CO, 80204, USA

      Xing Zhang

    3. Department of Chemistry and Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA

      Nathaniel S. Schocker, Jamal Khamsi, Roger A. Ashmus & Katja Michael

    4. Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA

      Igor C. Almeida

    5. Center for Biomedical Mass Spectrometry, Boston University School of Medicine, 670 Albany Street, Boston, MA, 02118, USA

      Catherine E. Costello

    Authors
    1. Xueyun Zheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xing Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Nathaniel S. Schocker
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Ryan S. Renslow
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Daniel J. Orton
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Jamal Khamsi
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Roger A. Ashmus
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Igor C. Almeida
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Keqi Tang
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Catherine E. Costello
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Richard D. Smith
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Katja Michael
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Erin S. Baker
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Katja Michael or Erin S. Baker.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Additional information

    Published in the topical collection Glycomics, Glycoproteomics and Allied Topics with guest editors Yehia Mechref and David Muddiman.

    Xueyun Zheng and Xing Zhang contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    ESM 1

    (PDF 355 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zheng, X., Zhang, X., Schocker, N.S. et al. Enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses. Anal Bioanal Chem 409, 467–476 (2017). https://doi.org/10.1007/s00216-016-9866-4

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00216-016-9866-4

    Keywords

    Search

    Navigation