Analytica Chimica Acta 2015-01-15

A method for rapid screening of interactions of pharmacologically active compounds with albumin.

Aldona Majcher, Anna Lewandrowska, Franciszek Herold, Jacek Stefanowicz, Tomasz Słowiński, Aleksander P Mazurek, Stefan A Wieczorek, Robert Hołyst

文献索引：Anal. Chim. Acta 855 , 51-9, (2014)

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摘要

We determine the association constants for ligand-protein complex formation using the flow injection method. We carry out the measurements at high flow rates (F=1 mL min(-1)) of a carrier phase. Therefore, determination of the association constant takes only a few minutes. Injection of 1 nM of the ligand (10 μL of 1 μM concentration of the ligand solution) is sufficient for a single measurement. This method is tested and verified for a number of complexes of selected drugs (cefaclor, etodolac, sulindac) with albumin (BSA). We obtain K=4.45×10(3) M(-1) for cefaclor, K=1.00×10(5) M(-1) for etodolac and K=1.03×10(5) M(-1) for sulindac in agreement with the literature data. We also determine the association constants of 20 newly synthesized 3β- and 3α-aminotropane derivatives with potential antipsychotic activity--ligands of 5-HT1A, 5-HT2A and D2 receptors with the albumin. Results of the studies reported here indicate that potential antipsychotic drugs bind weakly to the transporter protein (BSA) with K≈10(2)-10(3) M(-1). Our method allows measuring K in a wide range of values (10(2)-10(9) M(-1)). This range depends only on the solubility of the ligand and sensitivity of the detector.Copyright © 2014 Elsevier B.V. All rights reserved.