Site I on human albumin: differences in the binding of (R)- and (S)-warfarin.
The binding of drugs known to interact with area I on human serum albumin (HSA) was investigated using a chiral stationary phase obtained by anchoring HSA to a silica matrix. In particular, this high-pressure affinity chromatography selector was employed to study the binding properties of the individual enantiomers of warfarin. The pH and composition of the mobile phase modulate the enantioselective binding of warfarin. Displacement chromatography experiments evidenced significant differences in the binding of the warfarin enantiomers to site I. The (S)-enantiomer was shown to be a direct competitor for (R)-warfarin, while (R)-warfarin was an indirect competitor for the (S)-enantiomer. Salicylate directly competed with (R)-warfarin and indirectly with (S)-warfarin. This behavior was confirmed by difference CD experiments, carried out with the same [HSA]/[drug] system in solution.
Bertucci
C
C
Centro Studio CNR Macromolecole Stereordinate ed Otticamente Attive, Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Pisa, Italy. brtcrl@dcci.unipi.it
Canepa
A
A
Ascoli
G A
GA
Guimaraes
L F
LF
Felix
G
G
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D006801:Humans; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014859:Warfarin / Q000378:metabolism* / Q000592:standards
D012709:Serum Albumin; D014859:Warfarin