Study of interaction of pranoprofen with human serum albumin: binding properties of enantiomers and metabolite.

Abstract

The interaction of pranoprofen, pranoprofen glucuronide and pranoprofen methylester with human serum albumin (HSA), was investigated by equilibrium dialysis and spectroscopic techniques. The binding affinities of pranoprofen glucuronide and pranoprofen methylester to HSA were found to be almost the same, although they were remarkably small as compared to that of the parent compound, pranoprofen. Pranoprofen and pranoprofen methylester showed stereoselective affinities to HSA. It was found from the competitive displacement experiments using the fluorescent probes that the specific binding site for pranoprofen was site II, the diazepam site, and that the binding sites of pranoprofen glucuronide and pranoprofen methylester were site I, the warfarin site. In addition, from the binding data with modified HSA, it seemed that tyrosine-411 was specifically involved in the pranoprofen binding. The absorption spectral changes which accompanied the binding of pranoprofen and pranoprofen methylester to HSA or detergents implied that the HSA binding site of pranoprofen consisted of a cationic site on the surface of the albumin molecule with a hydrophobic region to accommodate the aromatic ring and that the binding site for pranoprofen methylester seemed to occupy a wide hydrophobic area. These limited data indicated differences in the location and microenvironments of binding sites for pranoprofen and its glucuronide on the HSA molecule.