title: A method for rapid screening of interactions of pharmacologically active compounds with albumin.
abstract: 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.
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Aldona
authors.initials: A
authors.lastname: Majcher
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lewandrowska
authors.affiliation: Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Franciszek
authors.initials: F
authors.lastname: Herold
authors.affiliation: Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Stefanowicz
authors.affiliation: Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Słowiński
authors.affiliation: Department of Drug Chemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland; National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Wieczorek
authors.affiliation: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland. Electronic address: rholyst@ichf.edu.pl.
authors.forename: Robert
authors.initials: R
authors.lastname: Hołyst
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism; D002417:Cattle; D002433:Cefaclor / Q000378:metabolism; D017308:Etodolac / Q000378:metabolism; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013467:Sulindac / Q000378:metabolism; D013997:Time Factors; D014326:Tropanes / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D008024:Ligands; D004364:Pharmaceutical Preparations; D014326:Tropanes; D013467:Sulindac; D012710:Serum Albumin, Bovine; D017308:Etodolac; D002433:Cefaclor
keywords: Association constant; Drug–protein interactions; Potential drugs; Taylor dispersion analysis