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Tandem mass spectrometry of glycosaminoglycans

Structural characterization of highly sulfated glycosaminoglycan (GAG) by collisionally activated dissociation (CAD) is challenging due to the extensive sulfate losses mediated by free protons. Removal of the free protons suffers problems such as low sensitivity, using high concentration of reagent that is not well compatible with common analytical instruments, and heterogeneity for both precursor ions and product ions. Electron detachment dissociation (EDD) has been proven to produce extensive informative fragmentation for GAG without removal of free protons. However, the efficiency of EDD gets lower for the anion with higher charge density and will eventually fail for the highly sulfated GAG. In this work, we improved the EDD efficiency by increasing the population of high-energy electrons and the cross-sections between electrons and anions. Results demonstrated that under the improved condition, EDD effectively fragmented a highly sulfated heparin-based drug, Arixtra, and other highly sulfated heparins. The charge state of the precursor ion does not significantly affect the occurrence of the structurally informative fragments. Further sensitivity test suggested EDD can fit in the liquid chromatography (LC) time-scale. All these improvements indicate the potential of the EDD technique for the more detailed and extensive analysis of highly sulfated GAG.

  • Huang, Y.; Yu, X.; Mao, Y.; Costello, C. E.; Zaia, J.; Lin, C. De Novo Sequencing of Heparan Sulfate Oligosaccharides by Electron-Activated Dissociation. Anal. Chem. 2013, 85, 11979-11986. Pubmed Link

  • Hu, H.; Huang, Y.; Mao, Y.; Yu, X.; Xu, Y.; Liu, J.; Zong, C.; Boons, G. J.; Lin, C.; Xia, Y.; Zaia, J. A Computational Framework for Heparan Sulfate Sequencing Using High-resolution Tandem Mass Spectra. Molecular & cellular proteomics : MCP 2014, 13, 2490-2502. Pubmed Link

  • Huang, Y.; Mao, Y.; Zong, C.; Lin, C.; Boons, G.; Zaia, J. Discovery of a Heparan Sulfate 3-O-Sulfation Specific Peeling Reaction. Anal. Chem. 2015, 81, 592-600. Pubmed Link

  • Huang, Y.; Mao, Y.; Buczek-Thomas, J. A.; Nugent, M. A.; Zaia, J. Oligosaccharide substrate preferences of human extracellular sulfatase sulf2 using liquid chromatography-mass spectrometry based glycomics approaches. PLoS ONE 2014, 9, e105143. Pubmed Link
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