BINDING POSITION OF TOLBUTAMIDE TO HUMAN SERUM-ALBUMIN

The interaction between drugs (tolbutamide (1), 1-butyl-3-(methylsulfo nyl)urea (2)) and human serum albumin (3) was investigated by equilibr ium dialysis and NMR spectroscopy. The binding of 1 and 2 to 3 was con cluded to be hydrophobic and hydrophilic, respectively, on the basis o f the dependence of the binding constants on temperature, ionic streng th, and chain length of fatty acid added. In H-1-NMR spectra of 1, the re were no significant shifts with change in concentration or addition of 3, The spin-lattice relaxation time (T-1) and spin-spin relaxation rate (1/T-2) of the respective protons of 1 were independent of conce ntration, but depended on the concentration of 3 added. The binding po sition was determined from the ratio of 1/T-2 of 1 bound to 3 and free 1. 1 and 2 were found to bind to 3 through the tolyl group and sulfon ylurea group, respectively. The binding property of 1 was considered t o be governed by the competition between the hydrophobic effect of the tolyl group and the hydrophilic effect of the sulfonylurea group in t he molecule.