Fu Li, Li Kevin, Mori Daisuke, Hirakane Makoto, Lin Lei, Grover Navdeep, Datta Payel, Yu Yanlei, Zhao Jing, Zhang Fuming, Yalcin Murat, Mousa Shaker A, Dordick Jonathan S, Linhardt Robert J
The Pharmaceutical Research Institute, Albany College of Pharmacy , Rensselaer, New York 12144, United States.
Department of Physiology, Veterinary Medicine Faculty, Uludag University , Gorukle 16059, Bursa, Turkey.
J Med Chem. 2017 Oct 26;60(20):8673-8679. doi: 10.1021/acs.jmedchem.7b01269. Epub 2017 Oct 16.
Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.
与美国药典（USP）猪肝素不同，牛肠肝素（BIH）的抗凝活性较低。用6-O-硫酸转移酶-1、-3和/或3-O-硫酸转移酶-1进行处理，得到了两种符合USP肝素活性和分子量规格的重塑肝素。我们在兔模型中探究了其药效学和药代动力学。我们得出结论，BIH中3-O-磺基含量的适度增加会增加抗凝血酶III结合位点的数量，使重塑后的BIH表现得与药用肝素相似。
