Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins

Xu, Y.
Masuko, S.
Takieddin, M.
Xu, H.
Liu, R.
Jing, J.
Mousa, S.
Linhardt, Robert J.
Liu, J.
Thumbnail Image
Other Contributors
Issue Date
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Terms of Use
In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
Full Citation
Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins, Y. Xu, S. Masuko, M. Takieddin, H. Xu, R. Liu, J. Jing, S. Mousa, R. J. Linhardt, J. Liu, Science, 334, 498-501, 2011.
Ultralow molecular weight (ULMW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent.
Science, 334, 498-501
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
A full text version is available in DSpace@RPI