Study on the binding of dicumarol to .ALPHA.1-acid glycoprotein using circular dichroism spectroscopy.

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Abstract
The interaction of dicumarol with .alpha.1-acid glycoprotein (.alpha.1-AGP) was studied by circular dichroism measurements. A single site having a binding constant of 2.9 .times. 105 M-1 was capable of inducing optical activity in dicumarol. The induced ellipticity of the dicumarol-.alpha.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 .alpha.1-AGP. The displacement of dicumarol from .alpha.1-AGP by fatty acids and neutral salts suggested a hydrophobic force to be involved in the binding. Interestingly, dicumarol was displaced by acidic drugs 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 20 .ANG. in depth.