Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
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Synthetic oligosaccharides can replace animal-sourced low-molecular weight heparins, Y. Xu, K. Chandarajoti, X. Zhang, V. Pagadala, W. Dou, D. M. Hoppensteadt, E. Sparkenbaugh, B. Cooley, S. Daily, N. S. Key, D. Severynse-Stevens, J. Fareed, R. J. Linhardt, R. Pawlinski, J. Liu, Science Translational Medicine, 9, eaan5954, 2017.
Low-molecular weight heparin (LMWH) is used clinically to treat clotting disorders. As an animal-sourced product, LMWH is a highly heterogeneous mixture, and its anticoagulant activity is not fully reversible by protamine. Furthermore, the reliability of the LMWH supply chain is a concern for regulatory agencies. We demonstrate the synthesis of heparin dodecasaccharides (12-mers) at the gram scale. In vitro experiments demonstrate that the anticoagulant activity of the 12-mers could be reversed using protamine. One of these, labeled as 12-mer-1, reduced the size of blood clots in the mouse model of deep vein thrombosis and attenuated circulating procoagulant markers in the mouse model of sickle cell disease. An ex vivo experiment demonstrates that the anticoagulant activity of 12-mer-1 could be reversed by protamine. 12-mer-1 was also examined in a nonhuman primate model to determine its pharmacodynamic parameters. A 7-day toxicity study in a rat model showed no toxic effects. The data suggest that a synthetic homogeneous oligosaccharide can replace animal-sourced LMWHs.;
Science Translational Medicine, 9, eaan5954; 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.
The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
American Association for the Advancement of Science (AAAS)
The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Science Translational Medicine; https://harc.rpi.edu/;