Assignment of hexuronic acid stereochemistry in synthetic heparan sulfate tetrasaccharides with 2-O-sulfo uronic acids using electron detachment dissociation

Isaac Agyekum, Anish B. Patel, Chengli Zong, Geert Jan Boons, I. Jonathan Amster*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    The present work focuses on the assignment of uronic acid stereochemistry in heparan sulfate (HS) oligomers. The structural elucidation of HS glycosaminoglycans is the subject of considerable importance due to the biological and biomedical significance of this class of carbohydrates. They are highly heterogeneous due to their non-template biosynthesis. Advances in tandem mass spectrometry activation methods, particularly electron detachment dissociation (EDD), have led to the development of methods to assign sites of sulfo modification in glycosaminoglycan oligomers, but there are few reports of the assignment of uronic acid stereochemistry, necessary to distinguish glucuronic acid (GlcA) from iduronic acid (IdoA). While preceding studies focused on uronic acid epimers with no sulfo modification, the current work extends the assignment of the hexuronic acid stereochemistry to 2-O-sulfo uronic acid epimeric tetrasaccharides. The presence of a 2-O-sulfo group on the central uronic acid was found to greatly influence the formation of B3, C2, Z2, and Y1 ions in glucuronic acid and Y2 and 1,5X2 for iduronic acid. The intensity of these peaks can be combined to yield diagnostic ratios (DR), which can be used to confidently assign the uronic acid stereochemistry.

    Original languageEnglish
    Article number15488
    Pages (from-to)163-169
    Number of pages7
    JournalInternational Journal of Mass Spectrometry
    Volume390
    DOIs
    Publication statusPublished - 28 Aug 2015

    Keywords

    • Carbohydrates
    • Electron detachment dissociation
    • Epimers
    • FTICR
    • Glycosaminoglycans
    • Principal component analysis

    Fingerprint

    Dive into the research topics of 'Assignment of hexuronic acid stereochemistry in synthetic heparan sulfate tetrasaccharides with 2-O-sulfo uronic acids using electron detachment dissociation'. Together they form a unique fingerprint.

    Cite this