title: Interactions of human serum albumin with meloxicam: characterization of binding site.
abstract: Human serum albumin (HSA) is the most prominent protein in plasma. The three-domain design of HSA provides a variety of binding sites for many ligands, including heme, bilirubin and drugs. Here, we report the effect of new generation, non-steroidal anti-inflammatory drug (NSAID) meloxicam on the albumin conformation and ligand binding. In the present work the interaction of meloxicam with HSA in aqueous solution at physiological pH has been investigated through circular dichroism and fluorescence spectroscopy. The strong quenching of the fluorescence clearly indicated that the binding of the drug to HSA changed the microenvironment of tryptophan residue and the tertiary structure of HSA. This was confirmed by the destabilization of the warfarin binding site. CD and fluorescence spectroscopic results showed marked reductions (about 40% decrease in the CD Cotton effect intensity, and approximately 15% decrease of the fluorescence intensity) in the affinity of albumin for bilirubin upon meloxicam binding. The strong inhibition of warfarin and ANS bound to protein after meloxicam modification compared with aspirin confirms that the binding site of both drugs is not the same.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Wrocław Medical University, Szewska 38, 50-139 Wrocław, Poland. ltl@wchuwr.pl
authors.forename: Lilianna
authors.initials: L
authors.lastname: Trynda-Lemiesz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wiglusz
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism*; D001241:Aspirin / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D000077239:Meloxicam; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013843:Thiazines / Q000737:chemistry* / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism*; D014859:Warfarin / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008024:Ligands; D012709:Serum Albumin; D013843:Thiazines; D013844:Thiazoles; D014867:Water; D014859:Warfarin; D001241:Aspirin; D001663:Bilirubin; D000077239:Meloxicam