Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.
Nat Chem Biol. 2014 Apr;10(4):248-50. doi: 10.1038/nchembio.1459. Epub 2014 Feb 23.
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.
低分子量肝素 (LMWHs) 是一种基于碳水化合物的抗凝剂,临床上用于治疗血栓性疾病,但杂质、结构异质性或功能不可逆性可能会限制治疗选择。我们报告了一系列通过经济高效的化学酶法制备的合成 LMWHs。使用鱼精蛋白,一种特定的合成 LMWH 对人因子 Xa(FXa)的高活性在体外和体内是可逆的,这表明合成可及的构建体在下一代 LMWHs 中可以发挥关键作用。