RT Journal Article
SR Electronic
T1 Characterization of an important drug binding area on human serum albumin including the high-affinity binding sites of warfarin and azapropazone.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 387
OP 393
VO 21
IS 2
A1 K J Fehske
A1 U Schläfer
A1 U Wollert
A1 W E Müller
YR 1982
UL http://molpharm.aspetjournals.org/content/21/2/387.abstract
AB This paper reports a variety of experimental observations which strongly support the assumption that the warfarin binding site, or site I of human serum albumin, is better described as the warfarin-azapropazone binding area, consisting of the overlapping binding sites for warfarin and azapropazone. In general, drugs interacting with one of the two sites will also displace drugs bound to the other site, although their displacing potencies for both sites may vary considerably. This is most pronounced in the case of glibenclamide, which strongly inhibits the binding of drugs to the azapropazone site with only minor effects on drugs bound to the warfarin site. The lone tryptophan residue of human serum albumin, previously shown to be part of the warfarin binding site, is obviously located in the not-overlapping part of the warfarin site, so that its modification affects only the binding of drugs to the warfarin and not to the azapropazone site of this large binding area. The observation of different but overlapping binding sites might explain the fact that the albumin binding of drugs which seem to be bound to similar sites because of their mutual displacement can be affected differently during several disease states.