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Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides

  • Jiandong Wu
  • Juan Wei
  • John D. Hogan
  • Pradeep Chopra
  • Apoorva Joshi
  • Weigang Lu
  • Joshua Klein
  • Geert-Jan Boons
  • Cheng Lin
  • Joseph Zaia
Focus: Mass Spectrometry in Glycobiology and Related Fields: Research Article
First Online:
Received:
Revised:
Accepted:

Abstract

Among dissociation methods, negative electron transfer dissociation (NETD) has been proven the most useful for glycosaminoglycan (GAG) sequencing because it produces informative fragmentation, a low degree of sulfate losses, high sensitivity, and translatability to multiple instrument types. The challenge, however, is to distinguish positional sulfation. In particular, NETD has been reported to fail to differentiate 4-O- versus 6-O-sulfation in chondroitin sulfate decasaccharide. This raised the concern of whether NETD is able to differentiate the rare 3-O-sulfation from predominant 6-O-sulfation in heparan sulfate (HS) oligosaccharides. Here, we report that NETD generates highly informative spectra that differentiate sites of O-sulfation on glucosamine residues, enabling structural characterizations of synthetic HS isomers containing 3-O-sulfation. Further, lyase-resistant 3-O-sulfated tetrasaccharides from natural sources were successfully sequenced. Notably, for all of the oligosaccharides in this study, the successful sequencing is based on NETD tandem mass spectra of commonly observed deprotonated precursor ions without derivatization or metal cation adduction, simplifying the experimental workflow and data interpretation. These results demonstrate the potential of NETD as a sensitive analytical tool for detailed, high-throughput structural analysis of highly sulfated GAGs.

Graphical Abstract

Keywords

Negative electron transfer dissociation Fourier transform ion cyclotron resonance mass spectrometry Glycosaminoglycan Heparan sulfate Sulfation Glycomics 
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Notes

Funding Information

This work was supported by NIH grants P41GM104603, R21HL131554, and U01CA221234.

Supplementary material

13361_2018_1907_MOESM1_ESM.pdf (1.8 mb)
ESM 1 (PDF 1849 kb)

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Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Center for Biomedical Mass Spectrometry, Department of Biochemistry and Center for Biomedical Mass SpectrometryBoston University School of MedicineBostonUSA
  2. 2.Bioinformatics ProgramBoston UniversityBostonUSA
  3. 3.Complex Carbohydrate Research CenterUniversity of GeorgiaAthensUSA
  4. 4.Department of ChemistryUniversity of GeorgiaAthensUSA
  5. 5.Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Bijvoet Center for Biomolecular ResearchUtrecht UniversityUtrechtNetherlands

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