Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin

Fu L., Li K., Mori D., Hirakane M., Lin L., Grover N., ...More

JOURNAL OF MEDICINAL CHEMISTRY, vol.60, no.20, pp.8673-8679, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 60 Issue: 20
  • Publication Date: 2017
  • Doi Number: 10.1021/acs.jmedchem.7b01269
  • Journal Name: JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.8673-8679
  • Bursa Uludag University Affiliated: Yes

Abstract

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.