Chemical modification of hyaluronidase regulates its inhibition by heparin.

Chemical modification of surface amino groups of bovine testicular hyaluronidase with aldehyde dextran was conducted. It was found that with the increase of modification degree of hyaluronidase amino groups the value of residual enzymatic catalytic activity is decreased rather monotonously. It turned out that the value of inhibition of enzyme activity by heparin considerably depends on modification degree of enzyme. This dependence is of a threshold character. Sharp conformational changes in the enzyme occurring at 70-90% degree of its modification considerably lowers heparin inhibition. The higher the degree of hyaluronidase modification, the weaker its inhibition by heparin. More completely/deeply modified derivatives of hyaluronidase (modification degree 96-100%) are practically not inhibited by heparin. Thus, chemical conjugation of hyaluronidase with aldehyde dextran regulates the value of enzyme inhibition by heparin. Hyaluronidase modification becomes an informative tool to study the mechanism of inhibition of its enzyme activity and an efficient means for the development of new therapeutic preparations improving tissue permeability during cardiovascular injuries.