title: Specific ligand binding on genetic variants of human alpha1-acid glycoprotein studied by circular dichroism spectroscopy.
abstract: Human alpha1-acid glycoprotein displays genetic polymorphism. Different drug binding properties of the two main genetic products (F1-S and A variants) have been demonstrated. In search for specific circular dichroism (CD) probes, dicumarol and acridine orange were found to specifically bind to the F1-S and A variants, respectively. Dicumarol binding to the F1-S variant produced induced Cotton effects originating from the favored chiral conformation of the bound label. Acridine orange gave induced biphasic Cotton effects due to chiral intermolecular exciton interaction between label molecules bound to the A variant. Displacement of the CD probes by specific marker ligands was demonstrated. The induced CD spectrum of dicumarol was found to change sign in the presence of imipramine, as a manifestation of high-affinity ternary complex formation on the F1-S variant.
authors.affiliation: Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525, Budapest, Hungary
authors.forename: Ilona
authors.initials: I
authors.lastname: Fitos
authors.forename: Júlia
authors.initials: J
authors.lastname: Visy
authors.forename: Ferenc
authors.initials: F
authors.lastname: Zsila
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bikádi
authors.forename: György
authors.initials: G
authors.lastname: Mády
authors.forename: Miklós
authors.initials: M
authors.lastname: Simonyi
mesh_terms: D000165:Acridine Orange / Q000494:pharmacology; D001665:Binding Sites; D002942:Circular Dichroism / Q000379:methods*; D001728:Dicumarol / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D014644:Genetic Variation; D006801:Humans; D008024:Ligands; D009961:Orosomucoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D009961:Orosomucoid; D014475:Uncoupling Agents; D001728:Dicumarol; D000165:Acridine Orange