The influence of molecular weight on the biological activity of heparin like sulphated hyaluronic acids

Sulphated hyaluronic acids having a sulphation degree of 3.5 per disaccharide unit, HyalS(3.5), were prepared with different molecular weights corresponding to 21 x 10(3), 320 x 10(3) and 3500 x 10(3). The thrombin 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 concentrations. The thrombin time in plasma depended on the length of the chain, and the two lower MW HyalS(3.5) inhibited thrombin both by direct aspecific interaction and via HC II, whereas the activity of the highest MW compound was mainly related to the electrostatic interaction with HC II. The inactivation of FXa serine protease was only attributed to HyalS(3.5)-AT III complex. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.