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• W2076806500 abstract "Heparin and the low molecular weight heparins are extensively used as medicinal products to prevent and treat the formation of venous and arterial thrombi. In early 2008, administration of some heparin lots was associated with the advent of severe adverse effects, indicative of an anaphylactoid-like response. Application of orthogonal analytical tools enabled detection and identification of the contaminant as oversulfated chondroitin sulfate (OSCS) was reported in our earlier report. Herein, we investigate whether enzymatic depolymerization using the bacterially derived heparinases, given the structural understanding of their substrate specificity, can be used to identify the presence of OSCS in heparin. We also extend this analysis to examine the effect of other persulfonated glycosaminoglycans (GAGs) on the action of the heparinases. We find that all persulfonated GAGs examined were effective inhibitors of heparinase I, with IC50 values ranging from approximately 0.5–2 μg/mL. Finally, using this biochemical understanding, we develop a rapid, simple assay to assess the purity of heparin using heparinase digestion followed by size-exclusion HPLC analysis to identify and quantify digestion products. In the context of the assay, we demonstrate that less than 0.1% (w/w) of OSCS (and other persulfonated polysaccharides) can routinely be detected in heparin." @default.
• W2076806500 created "2016-06-24" @default.
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• W2076806500 date "2011-09-19" @default.
• W2076806500 modified "2023-09-26" @default.
• W2076806500 title "Competitive Inhibition of Heparinase by Persulfonated Glycosaminoglycans: A Tool to Detect Heparin Contamination" @default.
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• W2076806500 doi "https://doi.org/10.1021/ac201498a" @default.
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