Oversulfated chondroitin sulfate interaction with heparin-binding proteins: New insights into adverse reactions from contaminated heparins

Li, Boyangzi
Suwan, Jiraporn
Martin, Jeffrey G.
Zhang, Fuming
Zhang, Zhenqing
Hoppensteadt, Debra
Clark, Melanie
Fareed, Jawed
Linhardt, Robert J.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Oversulfated chondroitin sulfate interaction with heparin-binding proteins: New insights into adverse reactions from contaminated heparins, B. Li, J.Suwan, J.G. Martin, F. Zhang, Z. Zhang, D. Hoppensteadt, M. Clark, J. Fareed, R.J. Linhardt, Biochemical Pharmacology, 78, 292–300, 2009.
An oversulfated chondroitin sulfate (OSCS) was identified as a contaminant to pharmaceutical heparin and severe anaphylactoid reactions were ascribed to this contaminant. An examination of the biochemistry underlying both the anticoagulant activity and the toxic effects of oversulfated chondroitin sulfate was undertaken. This study demonstrates that the anticoagulant activity of this oversulfated chondroitin sulfate is primarily dependent on heparin cofactor II mediated inhibition of thrombin. Heparin and oversulfated chondroitin sulfate binding to coagulation, kinin-kallikrein and complement proteins were studied by surface plasmon resonance. While oversulfated chondroitin sulfate binds tightly to antithrombin III, unlike heparin, OSCS does not induce antithrombin III to undergo the conformational change required for its inactivation of thrombin and factor Xa. In contrast to heparin, oversulfated chondroitin sulfate tightly binds factor XIIa suggesting a biochemical mechanism for the factor XIIa-based enhancement of vasoactive bradykinin production.
Biochemical Pharmacology, 78, 292–300
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Biochemical Pharmacology
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