Neutralizing the anticoagulant activity of ultra-low molecular weight heparins using N-acetylglucosamine 6-sulfatase

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Authors
Zhou, Xianxuan
Li, Lingyun
Linhardt, Robert J.
Liu, Jian
Issue Date
2013-05-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Heparin has been the most commonly used anticoagulant drug for nearly a century. The drug heparin is generally categorized into three forms according to its molecular weight: unfractionated (UF, average molecular weight 13 000), low molecular weight (average molecular weight 5000) and ultra-low-molecular-weight heparin (ULMWH, average molecular weight 2000). An overdose of heparin may lead to very dangerous bleeding in patients. Protamine sulfate may be administered as an antidote to reverse heparin's anticoagulant effect. However, there is no effective antidote for ULMWH. In the current study, we examine the use of human N-acetylglucosamine 6-sulfatase (NG6S), expressed in Chinese hamster ovary cells, as a reversal agent for ULMWH. NG6S removes a single 6-O-sulfo group at the non-reducing end of the ULMWH Arixtra(®) (fondaparinux), effectively removing its ability to bind to antithrombin and preventing its inhibition of coagulation factor Xa. These results pave the way to developing human NG6S as an antidote for neutralizing the anticoagulant activity of ULMWHs.
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FEBS Journal, 280, 2523–2532
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Full Citation
Neutralizing the anticoagulant activity of ultra-low molecular weight heparins using N-acetylglucosamine 6-sulfatase, X. Zhou, L. Li, R. J. Linhardt, J. Liu, FEBS Journal, 280, 2523–2532, 2013.
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FEBS Press
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ISSN
17424658
1742464X
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