Study on the Binding of Dicumarol to α_1-Acid Glycoprotein Using Circular Dichroism Spectroscopy

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The interaction of dicumarol with α_1-acid glycoprotein (α_1-AGP) was studied by circular dichroism measurments, A sigle site having a binding constant of 2.9×10^5M^<-1> was capable of inducing optical activity in dicumarol. The induced ellipticity of the dicumarol-α_1-AGP complex was decreased by raising the pH from 6.0 to 9.0,reflecting the changes in the molecular species of the drug and the microenvironmental changes in α_1-AGP. The displacement of dicumarol from α_1-AGP by fatty acids and neutral salts suggested a hydrophobic force to be involved in the binding. Interestingly, dicumarol was displace by acidic durgs that bind to the binding site on human serum albumin called site I, or the warfarin site, whereas site II acidic drugs did not displace any dicumarol. Simple attempts to correlate displacement of dicumarol by p-aminobenzoates with the molecular size of a series of p-aminobenzoates suggested that the drug binding site is a hydrophobic cleft about 20Å in depth.
社団法人日本薬学会の論文
1988-12-25