AuthorLi, Boyangzi; Suwan, Jiraporn; Martin, Jeffrey G.; Zhang, Fuming; Zhang, Zhenqing; Hoppensteadt, Debra; Clark, Melanie; Fareed, Jawed; Linhardt, Robert J.
SubjectBiology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
Full CitationOversulfated 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.
AbstractAn 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.;
DescriptionBiochemical Pharmacology, 78, 292–300; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
DepartmentThe Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
RelationshipsThe Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Biochemical Pharmacology; https://harc.rpi.edu/;
AccessA full text version is available in DSpace@RPI;