High-Field Asymmetric-Waveform Ion Mobility Spectrometry and Electron Detachment Dissociation of Isobaric Mixtures of Glycosaminoglycans

  • Muchena J. Kailemia
  • Melvin Park
  • Desmond A. Kaplan
  • Andre Venot
  • Geert-Jan Boons
  • Lingyun Li
  • Robert J. Linhardt
  • I. Jonathan Amster
Research Article

Abstract

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is shown to be capable of resolving isomeric and isobaric glycosaminoglycan negative ions and to have great utility for the analysis of this class of molecules when combined with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and tandem mass spectrometry. Electron detachment dissociation (EDD) and other ion activation methods for tandem mass spectrometry can be used to determine the sites of labile sulfate modifications and for assigning the stereochemistry of hexuronic acid residues of glycosaminoglycans (GAGs). However, mixtures with overlapping mass-to-charge values present a challenge, as their precursor species cannot be resolved by a mass analyzer prior to ion activation. FAIMS is shown to resolve two types of mass-to-charge overlaps. A mixture of chondroitin sulfate A (CSA) oligomers with 4–10 saccharides units produces ions of a single mass-to-charge by electrospray ionization, as the charge state increases in direct proportion to the degree of polymerization for these sulfated carbohydrates. FAIMS is shown to resolve the overlapping charge. A more challenging type of mass-to-charge overlap occurs for mixtures of diastereomers. FAIMS is shown to separate two sets of epimeric GAG tetramers. For the epimer pairs, the complexity of the separation is reduced when the reducing end is alkylated, suggesting that anomers are also resolved by FAIMS. The resolved components were activated by EDD and the fragment ions were analyzed by FTICR-MS. The resulting tandem mass spectra were able to distinguish the two epimers from each other.

Key words

FAIMS Electron detachment dissociation Glycosaminoglycans Fourier transform ion cyclotron resonance mass spectrometry Differential mobility spectrometry Fourier transform mass spectrometry Carbohydrates 

Notes

Acknowledgments

M.J.K., L.L., R.J.L., and I.J.A. gratefully acknowledge financial support from the National Institutes of Health, R01-GM038060. M.J.K., A.V., G.J.B., and I.J.A. gratefully acknowledge financial support from the National Institutes of Health, P41-GM103390. M.J.K. personally acknowledges Dr. Franklin Leach for useful discussions about mass spectrometry analysis of GAGs.

Supplementary material

13361_2013_771_MOESM1_ESM.doc (246 kb)
ESM 1 (DOC 246 kb)

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Copyright information

© American Society for Mass Spectrometry 2013

Authors and Affiliations

  • Muchena J. Kailemia
    • 1
  • Melvin Park
    • 2
  • Desmond A. Kaplan
    • 2
  • Andre Venot
    • 3
  • Geert-Jan Boons
    • 3
  • Lingyun Li
    • 4
  • Robert J. Linhardt
    • 4
  • I. Jonathan Amster
    • 1
  1. 1.Department of ChemistryUniversity of GeorgiaAthensUSA
  2. 2.Bruker DaltonicsBillericaUSA
  3. 3.Complex Carbohydrate Research CenterUniversity of GeorgiaAthensUSA
  4. 4.Department of Chemistry and Chemical Biology, Chemical and Biological Engineering, and BiologyRensselaer Polytechnic InstituteTroyUSA

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