Abstract
The bindings of tolbutamide and chlorpropamide to bovine serum albumin and to acetylated bovine serum albumin were studied by nuclear magnetic relaxation techniques in order to determine which protons of the drug molecules are involved in the interaction. The effects of the bovine serum albumin concentration and pH on the relaxation rate of each proton were examined. A marked increase in the relaxation rate of each proton was observed with the addition of bovine serum albumin or acetylated bovine serum albumin. Relatively large effects on the relaxation rates of the α-methylene group of tolbutamide and that of chlorpropamide were observed upon addition of bovine serum albumin and change of pH. It is suggested that the sulfonylurea moiety (-SO2NHCONH-) of both drugs is the major binding site, so that the relaxation rates of the nearby α-methylene protons are most affected. The next largest increase was in the relaxation rates of phenyl protons of both drugs, suggesting that the phenyl moiety might be another site of drug-protein interaction.
