The existence of conformationally labile (preformed) drug binding sites in human serum albumin as evidenced by optical rotation measurements.

Abstract

The ability of certain drugs to induce conformational changes in human serum albumin has been examined by differential optical rotation measurements at 233 nm. At drug:protein molar ratios ([D]/[P]) of unity, the optical rotation increased, decreased or remained the same depending on the drug used. The change in the optical rotatory dispersion (ORD) signal was investigated as a function of the drug concentration. Drug-protein interactions were relatively specific. There exists at least one, and possibly more, stable preformed high affinity sites for the binding of drugs to albumin. At low [D]/[P] ratios, the ORD titration curves suggest that the high affinity sites are conformationally labile and that the albumin molecule is flexible.