Wzorek Joanna, Bednarek Radosław, Watala Cezary, Boncler Magdalena
Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Lodz, Poland.
Department of Cytobiology and Proteomics, Medical University of Lodz, Lodz, Poland.
Front Pharmacol. 2021 Mar 11;12:638257. doi: 10.3389/fphar.2021.638257. eCollection 2021.
Concurrent administration of two drugs may complicate the management of acute coronary syndromes: competitive drug displacement diminishes drug binding and alters drug pharmacodynamics. We investigated the interaction of two antiplatelet compounds (PSB 0777 and cangrelor) with human serum albumin (HSA) to determine whether they compete with one another for the binding to albumin. Both examined compounds have been earlier claimed to bind to HSA (PSB 0777) or plasma proteins (cangrelor). Fluorescence spectroscopy, surface plasmon resonance spectroscopy and molecular modeling indicated that PSB 0777 and cangrelor interacted with HSA with moderate affinity (K∼10 M). The binding of cangrelor to HSA involved primarily hydrophobic interactions, while the interaction of PSB 0777 with HSA was driven by hydrophobic and electrostatic forces. It was found that PSB 0777 and cangrelor do not share the same binding site on the protein. Our findings highlight the importance of albumin in the transport of PSB 0777 and cangrelor and suggest that the antiplatelet activity of the examined compounds used in combination is not affected by competition-induced changes in drug binding to HSA.
竞争性药物置换会减少药物结合并改变药物的药效学。我们研究了两种抗血小板化合物（PSB 0777和坎格雷洛）与人血清白蛋白（HSA）的相互作用，以确定它们是否会相互竞争与白蛋白的结合。之前有人声称这两种被研究的化合物可与HSA（PSB 0777）或血浆蛋白（坎格雷洛）结合。荧光光谱法、表面等离子体共振光谱法和分子建模表明，PSB 0777和坎格雷洛与HSA以中等亲和力相互作用（K∼10 M）。坎格雷洛与HSA的结合主要涉及疏水相互作用，而PSB 0777与HSA的相互作用是由疏水和静电力驱动的。研究发现，PSB 0777和坎格雷洛在蛋白质上不共享相同的结合位点。我们的研究结果突出了白蛋白在PSB 0777和坎格雷洛转运中的重要性，并表明联合使用的被研究化合物的抗血小板活性不受药物与HSA结合竞争诱导变化的影响。
