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Molecular Pharmacology, Vol 12, 1052-1061, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Further Characterization of Specific Drug Binding Sites on Human Serum Albumin

G. SUDLOW 1, D. J. BIRKETT 1, and D. N. WADE 1

1 Department of Clinical Pharmacology, St. Vincent's Hospital, Sydney, New South Wales, 2010, Australia

The fluorescent probes 5-dimethylaminonaphthalene-1-sulfonamide and dansylsarcosine function as specific markers for two distinct binding sites for anionic drugs on human serum albumin (HSA). The binding of drugs to site I or II was detected by measuring the displacement of these probes. The results give an indication of some of the structural features required for binding at these sites. Stearic acid binding to HSA induced different conformational changes in the albumin at sites I and II, which were detected by changes in the fluorescence and/or strength of binding of probes specific for the two sites. This provides further evidence for qualitative differences between the two sites. The specificity of the sites for particular drugs, even at high drug to albumin ratios, was established, and the specificity and characteristics of the two sites on human adult and neonatal sera were shown to be similar to those on crystalline HSA.

Submitted on March 23, 1976
Accepted on June 2, 1976




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