Abstract

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.

Department(s)

Chemical and Biochemical Engineering

Comments

National Institutes of Health, Grant P41 GM104603

International Standard Serial Number (ISSN)

1520-6882; 0003-2700

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2023 American Chemical Society, All rights reserved.

Publication Date

19 Feb 2019

PubMed ID

30649866

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