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Analytical and Bioanalytical Chemistry

, Volume 411, Issue 20, pp 5033–5045 | Cite as

Advancing MSn spatial resolution and documentation for glycosaminoglycans by sulfate-isotope exchange

  • Qing Guo
  • Vernon N. ReinholdEmail author
Paper in Forefront

Abstract

Glycosaminoglycans (GAGs) are carbohydrate polyionic polymers that participate in a host of critically important biological processes. A significant difficulty in the comprehensive structural characterization of GAGs is the determination of specific sulfation position isomers. We chose to circumvent sulfate lability by its liberation followed by specific isotope exchange that makes it amenable to methylation, collisional induced dissociation, and MSn disassembly for a detailed structural characterization. A set of chemistries that include sulfate release, isotopic (CD3– and CD3–CO–) replacement, and methylation have been modified to yield a stable product ideal for sequencing by MSn. Disassembly of these samples provides a detailed read-out of sequence inclusive of all sulfation sites. As documenting steps, we applied these chemical modifications to a series of disaccharides and a synthetic GAG pentamer, Arixtra®. Upon disassembly, glycosidic and cross-ring cleavages define the monomer composition including individual sulfation positions. The N- and O-sulfates are differentiated by deuterium-containing mass compositions. The uronic methylesters do not significantly alter the fragmentation patterns. A fragment library of these products is being assembled as an adjunct to our larger fragment library, some 15 years in the making.

Keywords

Glycosaminoglycans Permethylation MSn Ion trap 

Notes

Acknowledgements

This work was supported by National Cancer Institute of National Institutes of Health (USA) through the Common Fund of Glycoscience (U01CA221215).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1899_MOESM1_ESM.pdf (1.6 mb)
ESM 1 (PDF 1642 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Glycomics Center, Department of Molecular, Cellular, and Biomedical SciencesUniversity of New HampshireDurhamUSA

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