Composition, sequencing and ion mobility mass spectrometry of heparan sulfatelike octasaccharide isomers differing in glucuronic and iduronic acid content
journal contributionposted on 18.11.2021, 20:15 by RL Miller, W Wei, Ralf SchwoererRalf Schwoerer, Olga ZubkovaOlga Zubkova, Peter TylerPeter Tyler, JE Turnbull, JA Leary
Here we report ion mobility mass spectrometry (IMMS) separation and tandem mass spectrometry (MS2) sequencing methods used to analyze and differentiate six synthetically produced heparin/heparan sulfate (HS)-like octasaccharide (dp8) isomeric structures. These structures are isomeric with regard to either glucuronic acid (GlcA) or iduronic acid (IdoA) residues at various positions. IMMS analysis showed that a fully GlcA structure exhibited a more compact conformation, whereas the fully IdoA structure was more extended. Interestingly, the change from IdoA to GlcA in specific locations resulted in strong conformational distortions. MS2 of the six isomers showed very different spectra with unique sets of diagnostic product ions. Analysis of MS2 product ion spectra suggests that the GlcA group correlated with the formation of a glycosidic product ion under lower energy conditions. This resulted in an earlier product ion formation and more intense product ions. Importantly, this knowledge enabled a complete sequencing of the positions of GlcA and IdoA in each of the four positions located in each unique dp8 structure.
Preferred citationMiller, R. L., Wei, W., Schwörer, R., Zubkova, O. V., Tyler, P. C., Turnbull, J. E. & Leary, J. A. (2015). Composition, sequencing and ion mobility mass spectrometry of heparan sulfatelike octasaccharide isomers differing in glucuronic and iduronic acid content. European Journal of Mass Spectrometry, 21(3), 245-254. https://doi.org/10.1255/ejms.1337
Journal titleEuropean Journal of Mass Spectrometry
Online publication date01/06/2015
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glycosaminoglycanheparan sulfateIMMSMS2electron detachment dissociationarrival time distributionglucuronic acididuronic-acidBinding SitesGlucuronic AcidHeparitin SulfateIduronic AcidIsomerismPolysaccharidesSequence AnalysisSpectrometry, Mass, Electrospray IonizationScience & TechnologyPhysical SciencesTechnologyPhysics, Atomic, Molecular & ChemicalSpectroscopyPhysicsELECTRON DETACHMENT DISSOCIATIONANTITHROMBIN-BINDING SEQUENCEGLYCOSAMINOGLYCAN TETRASACCHARIDESDERMATAN SULFATERESIDUESDOMAINSGROWTHOLIGOSACCHARIDESCONFORMATIONDYNAMICSAnalytical Chemistry