Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins
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Authors
Xu, Y.
Masuko, S.
Takieddin, M.
Xu, H.
Liu, R.
Jing, J.
Mousa, S.
Linhardt, Robert J.
Liu, J.
Issue Date
2011
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
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.
Description
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.
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.
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.
Publisher
American Association for the Advancement of Science (AAAS)