Fu, LiLi, KevinHirakane, MakotoLin, LeiGrover, NavdeepDatta, PayelYu, YanleiZhao, JingZhang, FumingMousa, Shaker A.Dordick, Jonathan S.Linhardt, Robert J.2022-11-032022-11-032017-10-26Fu, L. vd. (2017). ''Enzymatic generation of highly anticoagulant bovine intestinal heparin''. Journal of Medicinal Chemistry, 60(20), 8673-8679.0022-26231520-4804https://doi.org/10.1021/acs.jmedchem.7b01269https://pubs.acs.org/doi/10.1021/acs.jmedchem.7b01269?cookieSet=1http://hdl.handle.net/11452/29361Unlike 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.eninfo:eu-repo/semantics/openAccessPharmacology & pharmacyMolecular-weight heparinsChemoenzymatic synthesisInduced thrombocytopeniaPharmaceutical heparinsChondroitin sulfatePorcineBindingTissuesDrugsAnimalsAnticoagulantsCarbohydrate sequenceCattleEnzymesHeparinIntestinesMagnetic resonance spectroscopyRabbitsArticle0004141143000302-s2.0-8503244926686738679602028972371Chemistry, medicinalHeparan Sulfate; Heparosan; Glycosaminoglycans3 o sulfotransferase6 o sulfotransferaseAnticoagulant agentAntithrombin IIIBovine intestinal heparinHeparinSulfotransferaseUnclassified drugAnticoagulant agentEnzymeHeparinAnimal experimentAnimal modelAnticoagulationArticleBinding affinityBinding siteBioengineeringChemical compositionEnzyme modificationNonhumanProtein bindingAnimalBiosynthesisBovineCarbohydrate analysisChemistryIntestineLeporidaeMetabolismNuclear magnetic resonance spectroscopy