Evaluation of Selective Competitive Binding of Basic Drugs to [alpha]1-Acid Glycoprotein Variants

• Published in: Biological & pharmaceutical bulletin Vol. 33; no. 1; p. 95
• Main Authors: Ishizaki, Junko, Fukaishi, Akiko, Fukuwa, Chie, Yamazaki, Satoko, Tabata, Mayu, Ishida, Takuya, Suga, Yukio, Arai, Kunizo, Yokogawa, Koichi, Miyamoto, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Science and Technology Agency 01-01-2010
• ISSN: 0918-6158; 1347-5215

We examined the binding of various basic drugs to the F1S and A genetic variants of α1-acid glycoprotein (AGP), which were isolated from native human commercial AGP (total AGP) by chromatography on an immobilized copper(II) affinity adsorbent. The values of the dissociation constant (Kd) of some basic drugs with the F1S variant in equilibrium dialysis differed characteristically from those with the A variant. The selective binding to these variants was evaluated by measuring the displacement ratio of dicumarol bound to the F1S variant or that of acridine orange bound to the A variant, using circular dichroism spectroscopy. There was reasonably good agreement between the Kd values and displacement ratios. There was a characteristic difference between the values of inhibition constant (Ki) of basic drugs towards dipyridamole binding to F1S and towards disopyramide binding to A in total AGP. We found that the Ki values for dipyridamole binding were well correlated with the Kd values for the F1S variant, whereas those for disopyramide binding were well correlated with the Kd values for the A variant. In conclusion, the higher the affinity of basic drugs for AGP, the more they inhibit the binding of other basic drugs, and further, the inhibitory potency depends on the selectivity of binding to the AGP variants.