Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS
Glycosaminoglycans (GAGs) Play Vital Roles in Many Biological Processes and Are Naturally Present as Complex Mixtures of Polysaccharides with Tremendous Structural Heterogeneity, Including Many Structural Isomers. Mass Spectrometric Analysis of GAG Isomers, in Particular Highly Sulfated Heparin (Hep) and Heparan Sulfate (HS), is Challenging Because of their Structural Similarity and Facile Sulfo Losses during Analysis. Herein, We Show that Highly Sulfated Hep/HS Isomers May Be Resolved by Gated-Trapped Ion Mobility Spectrometry (Gated-TIMS) with Negligible Sulfo Losses. Subsequent Negative Electron Transfer Dissociation (NETD) Tandem Mass Spectrometry (MS/MS) Analysis of TIMS-Separated Hep/HS Isomers Generated Extensive Glycosidic and Cross-Ring Fragments for Confident Isomer Differentiation and Structure Elucidation. the High Mobility Resolution and Preservation of Labile Sulfo Modifications Afforded by Gated-TIMS MS Analysis Also Allowed Relative Quantification of Highly Sulfated Heparin Isomers. These Results Show that the Gated-TIMS-NETD MS/MS Approach is Useful for Both Qualitative and Quantitative Analysis of Highly Sulfated Hep/HS Compounds in a Manner Not Possible with Other Techniques.
J. Wei et al., "Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS," Analytical Chemistry, vol. 91, no. 4, pp. 2994 - 3001, American Chemical Society, Feb 2019.
The definitive version is available at https://doi.org/10.1021/acs.analchem.8b05283
Chemical and Biochemical Engineering
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19 Feb 2019
National Institutes of Health, Grant P41 GM104603