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

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.