Specific ligand binding on genetic variants of human alpha1-acid glycoprotein studied by circular dichroism spectroscopy.
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.
Fitos
Ilona
I
Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525, Budapest, Hungary
Visy
Júlia
J
Zsila
Ferenc
F
Bikádi
Zsolt
Z
Mády
György
G
Simonyi
Miklós
M
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
D005456:Fluorescent Dyes; D008024:Ligands; D009961:Orosomucoid; D014475:Uncoupling Agents; D001728:Dicumarol; D000165:Acridine Orange