title: Interactions of the carrier ligands of antidiabetic metal complexes with human serum albumin: a combined spectroscopic and separation approach with molecular modeling studies.
abstract: The specific binding of carrier ligands of antidiabetic vanadium(IV) and zinc(II) complexes into drug binding pockets of human serum albumin (HSA) has been investigated via displacement reactions of site markers such as warfarin and dansylglycine by different spectroscopic (fluorescence, circular dichroism, NMR) and separation methods (capillary zone electrophoresis, ultrafiltration-UV). Conditional stability constants of the ligands were calculated for the binding at sites I and II of HSA. Binding site I was found to be the primary binding site for 2,6-pyridine dicarboxylic acid (dipic) and picolinic acid (pic), and site II for 6-methylpicolinic acid (6-Mepic) and maltol, although dipic, 6-Mepic and pic displace both site markers at differing extents. The experimental data is complemented by protein-ligand docking calculations for dipic and 6-Mepic which support the observations.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, PO Box 440, H-6701 Szeged, Hungary. enyedy@chem.u-szeged.hu
authors.forename: Eva A
authors.initials: EA
authors.lastname: Enyedy
authors.forename: László
authors.initials: L
authors.lastname: Horváth
authors.forename: Anasztázia
authors.initials: A
authors.lastname: Hetényi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D019075:Electrophoresis, Capillary; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000302:isolation & purification; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000302:isolation & purification; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D014462:Ultrafiltration; D014466:Ultraviolet Rays; D014639:Vanadium / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D007004:Hypoglycemic Agents; D008024:Ligands; D009942:Organometallic Compounds; D012709:Serum Albumin; D014639:Vanadium; D015032:Zinc