Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin

J Med Chem. 2017 Oct 26;60(20):8673-8679. doi: 10.1021/acs.jmedchem.7b01269. Epub 2017 Oct 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticoagulants*
  • Carbohydrate Sequence
  • Cattle
  • Enzymes / metabolism*
  • Heparin / biosynthesis*
  • Heparin / chemistry
  • Heparin / pharmacokinetics
  • Heparin / pharmacology
  • Intestinal Mucosa / metabolism*
  • Magnetic Resonance Spectroscopy
  • Rabbits

Substances

  • Anticoagulants
  • Enzymes
  • Heparin