Fibrinolytic and Fibrinogenolytic Effects of Acyl Urokinase and Urokinase Combinations In Vitro

L. I. Mukhametova, R. B. Aisina,^# and S. D. Varfolomeev

^# Fax: +7 (495) 939-5417; e-mail: arb@enzyme.chem.msu.ru
Faculty of Chemistry, Moscow State University, Vorob'evy gory, Moscow, 119899 Russia

Received July 19, 2005; in final form, September 27, 2005

Abstract: The in vitro thrombolytic and side effects of double-strand urokinase-type plasminogen activator (tcu-PA), p-guanidinobenzoyltcu-PA (GB-tcu-PA), and their combinations were compared. The reversible blocking of the active site stabilizes GB-tcu-PA in human plasma and results in longer thrombolysis and lesser side effects than those of tcu-PA. However, the acylated activator displays a marked lag period of thrombolytic action. GB-tcu-PA and tcu-PA combinations (molar ratios 4 : 1 and 1 : 1) induce a prolonged and effective thrombolysis without the initial lag period at a low level of plasminogen, fibrinogen, and α₂-antiplasmin depletion in the plasma surrounding the clot.

Key words: agent combination, p-guanidinobenzoylurokinase, side effects, stability in plasma, thrombolysis, urokinase

Russian Journal of Bioorganic Chemistry 2006, 32 (4):345-351