RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.
Synthetic oligosaccharides can replace animal-sourced low-molecular weight heparins
Xu, Y., Chandarajoti, K., Zhang, X., Pagadala, V., Dou, W., Hoppensteadt, D. M., Sparkenbaugh, E. M., Cooley, B., Daily, S., Key, N. S., Severynse-Stevens, D., Fareed, J., Linhardt, R. J., Pawlinski, R., & Liu, J. (2017). Synthetic oligosaccharides can replace animal-sourced low-molecular weight heparins. Science Translational Medicine, 9(406), Article eaan5954. https://doi.org/10.1126/scitranslmed.aan5954
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.
