A new strategy for defining critical functional groups on heparan sulfate

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Zhengliang L WuRobert D Rosenberg

Abstract

Heparan sulfate (HS) is a sulfated polysaccharide present on cell surfaces and in the extracellular matrix. Accumulating evidence shows that HS plays key roles in many biological systems by interacting with various proteins in a structural-specific manner. Due to technical difficulties, however, the understanding of critical functional groups on HS for protein interaction is vague. We report a rapid, convenient, sensitive, and inexpensive strategy using in vitro modification with pure enzymes and gel mobility shift assay to study the subject. We demonstrated the requirements of 3-O, 6-O sulfates and the minimal length of oligosaccharide for antithrombin III (AT-III) binding. We regenerated the binding sites for AT-III on completely desulfated N-resulfated heparin and revealed the critical modification enzymes. This new strategy could be used to identify critical functional groups on HS and to generate HS library and biologically active HS, providing information applicable to the design of HS drugs, such as anticoagulant reagents and viral infection blockers. The binding assay with fibroblast growth factors and receptors confirmed the general usefulness of this approach.

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Citations

Sep 15, 2010·Analytical and Bioanalytical Chemistry·Vy M TranBalagurunathan Kuberan
Dec 7, 2007·Journal of the American Society for Mass Spectrometry·Zhenqing ZhangRobert J Linhardt
Feb 12, 2010·BMC Biotechnology·Zhengliang L WuWeiping Jiang
Jul 31, 2007·Future Oncology·Stephanie RoesslerXin Wei Wang
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Oct 22, 2004·Glycobiology·Nicholas T SeyfriedAndrew Almond
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Nov 7, 2003·The Journal of Biological Chemistry·Zhengliang L WuRobert D Rosenberg
Feb 27, 2003·The Journal of Biological Chemistry·Zhengliang L WuRobert D Rosenberg
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May 7, 2014·Glycobiology·Zhengliang L WuJoseph Zaia
May 7, 2010·Advances in Colloid and Interface Science·Emek Seyrek, Paul Dubin

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