THE INFLUENCE OF MOLECULAR-WEIGHT ON THE BIOLOGICAL-ACTIVITY OF HEPARIN-LIKE SULFATED HYALURONIC ACIDS

Sulphated hyaluronic acids having a sulphation degree of 3.5 per disac charide unit, HyalS(3.5), were prepared with different molecular weigh ts corresponding to 21 x 10(3), 320 x 10(3) and 3500 x 10(3). The thro mbin inhibition in plasma and in the presence of purified molecules, i .e. fibrinogen, antithrombin III (AT III) and heparin cofactor II (HC II), were studied for the three different MW compounds at different co ncentrations. The thrombin time in plasma depended on the length of th e chain, and the two lower MW HyalS(3.5) inhibited thrombin both by di rect aspecific interaction and via HC II, whereas the activity of the highest MW compound was mainly related to the electrostatic interactio n with HC II. The inactivation of FXa serine protease was only attribu ted to HyalS(3.5)-AT III complex. (C) 1998 Published by Elsevier Scien ce Ltd. All rights reserved.