Differentiation of 3-O-Sulfated Heparin Disaccharide Isomers: Identification of Structural Aspects of the Heparin CCL2 Binding Motif

The presence of 3-O-sulfated glucosamine residues in heparin or heparan sulfate plays a role in binding to antithrombin III and HSV infection. In this study, tandem mass spectrometry was used to differentiate between two heparin disaccharide isomers containing variable sulfate at C6 in a common disa...

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Bibliographic Details
Published in:Journal of the American Society for Mass Spectrometry 2009-04, Vol.20 (4), p.652-657
Main Authors: Meissen, John K., Sweeney, Matthew D., Girardi, Matthew, Lawrence, Roger, Esko, Jeffrey D., Leary, Julie A.
Format: Article
Language:English
Subjects:
Analytical Chemistry
Animals
Anticoagulants
Binding
Binding Sites
Bioinformatics
Biotechnology
Chemistry
Chemistry and Materials Science
Chemokine CCL2 - chemistry
CHO Cells
Cricetinae
Cricetulus
Differentiation
Disaccharides - chemistry
Glycosaminoglycans - chemistry
Heparan sulfate
Heparin - analogs & derivatives
Heparin - chemistry
Humans
Isomerism
Isomers
Mass spectrometry
Oligosaccharides - chemistry
Organic Chemistry
Protein Binding
Proteomics
Sulfates - chemistry
Tandem Mass Spectrometry - methods
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Summary:The presence of 3-O-sulfated glucosamine residues in heparin or heparan sulfate plays a role in binding to antithrombin III and HSV infection. In this study, tandem mass spectrometry was used to differentiate between two heparin disaccharide isomers containing variable sulfate at C6 in a common disaccharide and C3 in a more rare one. The dissociation patterns shown by MS 2 and MS 3 were clearly distinguishable between the isomers, allowing their differentiation and quantitation. Using this technique, we show that an octasaccharide with 11 sulfate groups with high affinity for inflammatory chemokine CCL2 does not contain 3-O-sulfated disaccharides. CID was used to distinguish between heparin disaccharide isomers containing or lacking 3-O-sulfation and applied to evaluate the involvement of 3-O-sulfation in the heparin/CCL2 interaction.
ISSN:1044-0305
1879-1123
DOI:10.1016/j.jasms.2008.12.002