title: Comparative spectroscopic studies on drug binding characteristics and protein surface hydrophobicity of native and modified forms of bovine serum albumin: possible relevance to change in protein structure/function upon non-enzymatic glycation.
abstract: The interaction between serum albumin (SA) and drugs has provided an interesting ground for understanding of drug effects, especially in drug distribution and drug-drug interaction on SA, in the case of multi-drug therapy. Determination of the impact of various factors on drug-protein interaction is especially important upon significant binding of drug to albumin. In the present study, the interaction of two drugs (furosemide and indomethacin) with native and modified albumins were investigated by using various spectroscopic methods. Fluorescence data indicated that 1:1 binding of drugs to bovine serum albumin (BSA) is associated with quenching of albumin intrinsic fluorescence. The Job's plot also confirmed that drug binds to BSA via mentioned stoichiometry. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between drug and albumin may change upon protein modification. The theoretical analyses also suggested some conformational changes of interacting side chains in subdomain IIA binding site (at the vicinity of W237), which were in good agreement with experimental data. Decrease of protein surface hydrophobicity (PSH) was also observed upon both albumin modification and drug binding.
authors.affiliation: Medical Biology Research Center, Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, P.O. Box 67145-1673, Kermanshah University of Medical Sciences, Kermanshah, Iran. rkhodarahmi@mbrc.ac.ir
authors.forename: Reza
authors.initials: R
authors.lastname: Khodarahmi
authors.forename: Seyyed Arash
authors.initials: SA
authors.lastname: Karimi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ashrafi Kooshk
authors.forename: Seyyed Abolghasem
authors.initials: SA
authors.lastname: Ghadami
authors.forename: Sirous
authors.initials: S
authors.lastname: Ghobadi
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Amani
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001665:Binding Sites; D002417:Cattle; D004232:Diuretics / Q000378:metabolism*; D005665:Furosemide / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D012710:Serum Albumin, Bovine; D005665:Furosemide; D007213:Indomethacin