Preparation of low molecular weight heparin from a remodeled bovine intestinal heparin

Authors
Baytas, Sultan N.
Varghese, Sony S.
Jin, Weihua
Yu, Yanlei
He, Peng
Douaisi, Marc
Zhang, Fuming
Brodfuehrer, Paul
Xia, Ke
Dordick, Jonathan S.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2021-02-25
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
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Full Citation
Preparation of low molecular weight heparin from a remodeled bovine intestinal heparin, S. N. Baytas, S. S. Varghese, W. Jin, Y. Yu, P. He, M. Douaisi, F. Zhang, P. Brodfreur, K. Xia, J. S. Dordick, R. J. Linhardt, Journal of Medicinal Chemistry, 64, 2242-2253, 2021.
Abstract
Bovine intestinal heparins are structurally distinct from porcine intestinal heparins and exhibit lower specific anticoagulant activity (units/mg). The reduced content of N-sulfo, 3-O-sulfo glucosamine, the central and critical residue in heparin’s antithrombin III binding site, is responsible for bovine intestinal heparin’s reduced activity. Previous studies demonstrate that treatment of bovine intestinal heparin with 3-O-sulfotransferase in the presence of 3′-phosphoadenosine-5′-phosphosulfate afforded remodeled bovine heparin with an enhanced activity reaching the United States Pharmacopeia’s requirements. Starting from this remodeled bovine intestinal heparin, we report the preparation of a bovine intestinal low molecular weight heparin having the same structural properties and anti-factor IIa and anti-factor Xa activities of Enoxaparin. Moreover, this bovine intestinal heparin-derived “Enoxaparin” showed comparable platelet factor-4 binding affinity, suggesting that it should exhibit similarly low levels of heparin induced thrombocytopeneia, HIT.
Description
Journal of Medicinal Chemistry, 64, 2242-2253
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Journal of Medicinal Chemistry
https://harc.rpi.edu/
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