Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Authors

• Yongmei Xu, University of North Carolina
• Chao Cai, Rensselaer Polytechnic Institute
• Kasemsiri Chandarajoti, University of North Carolina
• Po-Hung Hsieh, University of North Carolina
• Lingyun Li, Rensselaer Polytechnic Institute
• Truong Q. Pham, University of North Carolina
• Erica M. Sparkenbaugh, University of North Carolina
• Juzheng Sheng, Shandong University
• Nigel S. Key, University of North Carolina
• Rafal Pawlinski, University of North Carolina
• Edward N. Harris, University of Nebraska - LincolnFollow
• Robert J. LinhardtFollow
• Jian Liu, University of North CarolinaFollow

Document Type

Article

Date of this Version

2014

Citation

Nat Chem Biol. 2014 April ; 10(4): 248–250

Comments

© 2014 Nature America, Inc.

doi:10.1038/nchembio.1459.

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.