Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

具有可逆抗凝活性的均质低分子量肝素

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作者: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

Abstract

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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