[Covalent stretokinase-polyethylene glycol conjugates with increased stability and decreased side effects].

By variation of incubation time of streptokinase (SK) with activated polyethylene glycol (M 2 and 5 kDa, PEG2 and PEG5) it was obtained covalent SK-PEG2 and SK-PEG5 conjugates with different modification degrees of amino groups of protein and their properties were studied in vitro as compared with free SK. It was shown, that maximal stable and retaining 80% fibrinolytic activity SK-PEG2 and SK-PEG5 conjugates are formed when the modification degrees of amino groups of protein are 54 and 52%, respectively. At interaction of the given conjugates with equimolar plasminogen concentration it were formed the plasmin (Pm)·SK-PEG2 and Pm·SK-PEG5 activator complexes, the maximal amidase activity of which is equal to activity of unmodified Pm·SK complex. It was found, that the catalytic efficiency of plasminogen activation (kPg/KPg) by Pm·SK-PEG2 complex is some higher (2.84 min(-1) µM(-1)) and by Pm·SK-PEG5 complex is lower (1.17 min(-1) µM(-1)), than that by unmodified Pm·SK complex (2.1 min(-1) µM(-1)). Investigation of lysis kinetics of human plasma clots and depletion of plasminogen and fibrinogen in plasma under the action of free SK and SK-PEG2 and SK-PEG5 conjugates showed, that the latter's have high thrombolytic activity (89 and 72%, respectively) and cause 3.5-4 fold lower side effects, than free SK. Obtained by us SK-PEG2 and SK-PEG5 conjugates with increased stability and decreased side effects may be used in the therapy of thrombotic disorders.

[The thrombolytic activity of acylated activator complexes of plasmin-streptokinase with different rates of reactivation]. / Tromboliticheskaia aktivnost' atsilirovannykh aktivatornykh kompleksov plazmin--streptokinaza s razlichnymi skorostiami reaktivatsii.

In the experiments on guinea-pigs with venous thrombosis there were studied the fibrin- and thrombolytic effects of streptokinase, the plasmin-streptokinase complex and the acylated derivatives of the complex with various rates of reactivation. It was established that the acylated derivatives of the plasmin-streptokinase complex possess greater stability in the blood flow and lead to more prolonged stimulation of fibrinolysis at less magnitude of its systemic activation. Due to this the acylated derivatives of the plasmin-streptokinase complex produce less pronounced fibrinogenolysis. In connection with a high affinity to fibrin their thrombolytic action does not depend on the systemic activation of fibrinolysis.