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ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)

 5 2018

"Biotechnologia Acta" V. 11, No 5, 2018
Р. 26-34, Bibliography , English
Universal Decimal Classification: 577.151


O. I. Yusova, O. V. Savchuk, T. Yatsenko, V. Popadiuk, L. G. Kapustianenko, T. V. Grinenko

Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv

The aim of the work was to study plasmin inhibiting properties of calix[4]arenes functionalized by phosphonic acid remnants. The following methods were used: turbidimetry, analysis of enzyme activity for chromogenic substrates, evaluation of caseinolytic activity for the release of tyrosine from casein, Dixon’s method for determining the type and inhibition constant. It was found, that calix[4]arenes С 296, С-425, С-427 and C-145 inhibit fibrin clot lysis by plasmin in dose-dependent manner and inhibition rate is proportional to the number of phosphonic acid remnants. C-145 is a most effective plasmin inhibitor (competitive mechanism, Ki = 0,52 ?M). However, C-145, as well as С-296, С-425 and С-427, does not affect amidolytic and caseinolytic plasmin activity but inhibit plasminogen activation by streptokinase. Thus, we assume that the mechanism of calyx[4]arene selectivity to fibrinolysis and its ability to obstruct plasminogen-streptokinase interaction is provided by complex formation between calix[4]arene negatively charged phosphonic groups and positively charged amino acids in substrate recognition exosites of plasmin. Calix[4]arene C-145 is effective plasmin fibrinolytic activity inhibitor and perspective for further investigation as antifibrinolytic agent.

Key words: fibrinolysis, plasmin, plasminogen, plasmin inhibitor, plasminogen activation, streptokinase

© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2018