Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

February 23rd, 2014 by Yongmei Xu

Nature Chemical Biology 10, 248 (2014). doi:10.1038/nchembio.1459

Authors: Yongmei Xu, Chao Cai, Kasemsiri Chandarajoti, Po-Hung Hsieh, Lingyun Li, Truong Q Pham, Erica M Sparkenbaugh, Juzheng Sheng, Nigel S Key, Rafal Pawlinski, Edward N Harris, Robert J Linhardt & Jian Liu

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs.

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