Structural modification induced in heparin by a Fenton-type depolymerization process

Semin Thromb Hemost. 2007 Jul;33(5):466-77. doi: 10.1055/s-2007-982077.

Abstract

A low molecular weight heparin (LMWH) obtained by a depolymerization process induced by a Fenton-type reagent was characterized in depth by nuclear magnetic resonance (NMR) spectroscopy. The depolymerization involves the cleavage of glycosidic bonds, leading to natural terminal reducing end residues, mainly represented by N-sulfated glucosamine (A (NS)). Natural uronic acids, especially the 2- O-sulfate iduronic acid (I (2S)), are also present as reducing residues. A peculiar reaction results, such as the disappearance of the nonsulfated iduronic acid residues when followed by 6-O-nonsulfated glucosamine, and the decrease of the glucuronic acid when followed by the N-acetylglucosamine, were observed. Iduronic acid residues, followed by 6- O-sulfate glucosamine (A (Nx,6S)), and the glucuronic acid residues, followed by A (NS) residues, were not modified. A few minor internal chain modifications occur, possibly arising from oxidative breaking of the bond between C2-C3 of glucosamine and uronic acids, suggested by evidence of formation of new -COR groups. Finally, no change was observed in the content of the N-sulfated, 6-O-sulfated glucosamine bearing an extra sulfate on 3-O, which is considered the marker of the active site for antithrombin. With respect to the original heparin, this LMWH is characterized by a lower number of nonsulfated uronic acid residues, and as a consequence, by a lower degree of structural heterogeneity than LMWHs prepared with other procedures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Free Radicals / chemistry*
  • Heparin, Low-Molecular-Weight / chemistry*
  • Iduronic Acid / chemistry*
  • Molecular Structure
  • Oxidation-Reduction

Substances

  • Free Radicals
  • Heparin, Low-Molecular-Weight
  • Iduronic Acid