SULFATED POLYSACCHARIDE FROM THE LEAVES OF ARTEMISIA PRINCEPS ACTIVATES HEPARIN COFACTOR II INDEPENDENTLY OF THE LYS173 and ARG189 RESIDUES OF HEPARIN COFACTOR II

Abstract

A sulfated polysaccharide (AFE-HCD) purified from the leaves of Artemisia princeps Pamp selectively accelerated the rate of thrombin inhibition by heparin cofactor II (HCII). By using plasma derived HCII and bacterial expressed recombinant HCII molecules, the interaction between each HCII molecule and AFE-HCD was analyzed. AFE-HCD accelerated thrombin inhibition by plasma derived HCII or bacterial expressed wild type HCII to the same extent (IC50: 0.056 μg/ml for plasma derived HCII and 0.066 μg/ml for recombinant HCII under the experimental condition). The recombinant HCII (rHCII) molecule with Lys173 → Leu or Arg189 → His substitution, which is defective in interactions with heparin and dermatan sulfate, respectively, is activated by AFE-HCD to inhibit thrombin in a manner similar to wild type rHCII. These results suggested that activation of HCII was independent of its Lys173 or Arg189 residue. Although AFE-HCD is a selective activator of HCII like dermatan sulfate, the amino acid residue required for the activation of HCII was distinct from that of dermatan sulfate as well as heparin. © 1997 Elsevier Science Ltd