RT Journal Article
SR Electronic
T1 Optical Studies on the Mechanism of the Interaction of the Enantiomers of the Anticoagulant Drugs Phenprocoumon and Warfarin with Human Serum Albumin
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 70
OP 79
VO 13
IS 1
A1 NIGEL A. BROWN
A1 EBERHARD JÄHNCHEN
A1 WALTER E. MÜLLER
A1 UWE WOLLERT
YR 1977
UL http://molpharm.aspetjournals.org/content/13/1/70.abstract
AB The interaction of the racemates and enantiomers of phenprocoumon and warfarin with human serum albumin was investigated using equilibrium dialysis and circular dichroism measurements. It was found that the human serum albumin molecule binds phenprocoumon stereospecifically, with about a 2-fold higher association constant for the S(-)isomer. The stereospecificity of phenprocoumon binding is more pronounced than that of the warfarin enantiomers. Binding to human serum albumin induces Cotton effects in the enantiomers of phenprocoumon and warfarin, which superimpose upon the intrinsic Cotton effects of the drugs. The induced Cotton effects are similar in sign for the two phenprocoumon isomers, but dissimilar for the warfarin isomers. Therefore it is concluded that the orientation of the 4-hydroxycoumarin nucleus is the same for the phenprocoumon isomers, but different for the warfarin isomers, when bound to human serum albumin. This can explain differences in the stereoselective binding of the two drugs to human serum albumin. ACKNOWLEDGMENTS The excellent technical assistance of Miss Ulrike Bolz and Mrs. Krista Lemmel is gratefully acknowledged. The authors wish to thank Dr. John Flectcher, Laboratory of Applied Studies, Division of Computer Research and Technology, National Institutes of Health, for performing the nonlinear least-squares curve-fitting calculations.