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Journal of the Serbian Chemical Society 2009, vol. 74, br. 4, str. 379-388
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Inhibicija tripsina heparinom i dalteparinom
aUniverzitet u Beogradu, Medicinski fakultet, Institut za fiziologiju bInstitut za hemiju, Medicinski fakultet, Beograd cUniverzitet u Beogradu, Hemijski fakultet
e-adresa: kgopcevic@yahoo.com
Projekat Ministarstva nauke Republike Srbije, br. 142018B
SažetakU radu je ispitivana interakcija tripsina, kao prototipa S1 serin-proteaze, sa heparinom i njegovim niskomolekulskim derivatom dalteparinom fragminom. Utvrđena je direktna inhibicija tripsina kako heparinom tako i dalteparinom, u koncentracijama tipičnim za njihovu kliničku upotrebu. Određena je IC50 tripsina heparinom: 15,25±1,22 μg/mL i dalteparinom: 58,47±15,20 μg/mL. Kinetička analiza je pokazala da heparin i njegov niskomolekulski derivat dalteparin inhibiraju tripsin po modelu nekompetitivne i mešovite inhibicije, redom. Heparin sa konstantom inhibicije Ki1,2 =0,151±0,019 μM (nekompetitivna) i dalteparin sa Ki1 = 0,202±0,030 μM i Ki2 = 0,463±0,069 μM (mešovita), predstavljaju umerene inhibitore tripsina, kao referentne serin-proteaze. Dobijene konstante inhibicije ukazuju da pri klinički aplikovanim koncentracijama heparina i dalteparina, tripsini i homologe S1 serin-proteaze mogu biti direktno inhibirane i time uticati na delikatnu kontrolu aktivnosti serin-proteaza u homeostazi.
Ključne reči
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