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Homogeneous low-molecular-weight heparins with reversible anticoagulant activity
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Journal Article
Homogeneous low-molecular-weight heparins with reversible anticoagulant activity
2014
Overview
Heparin analogs can serve as potent anticoagulants, but heterogeneous structures in some preparations and lack of antidote for others can complicate treatments. A chemoenzymatic method that prevents reversible epimerization now enables reversible application of defined constructs in cells and mice.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 64/60
/ 82
/ Animals
/ Anticoagulants - antagonists & inhibitors
/ Anticoagulants - chemical synthesis
/ Anticoagulants - pharmacology
/ Antithrombins - pharmacology
/ Cell Adhesion Molecules, Neuronal - metabolism
/ Chromatography, High Pressure Liquid
/ Heparin, Low-Molecular-Weight - antagonists & inhibitors
/ Heparin, Low-Molecular-Weight - chemical synthesis
/ Heparin, Low-Molecular-Weight - pharmacology
/ Humans
/ Male
/ Mice
