Binding position of tolbutamide to human serum albumin.
The interaction between drugs (tolbutamide (1), 1-butyl-3-(methylsulfonyl)urea (2)) and human serum albumin (3) was investigated by equilibrium dialysis and NMR spectroscopy. The binding of 1 and 2 to 3 was concluded to be hydrophobic and hydrophilic, respectively, on the basis of the dependence of the binding constants on temperature, ionic strength, and chain length of fatty acid added. In 1H-NMR spectra of 1, there were no significant shifts with change in concentration or addition of 3. The spin-lattice relaxation time (T1) and spin-spin relaxation rate (1/T2) of the respective protons of 1 were independent of concentration, but depended on the concentration of 3 added. The binding position was determined from the ratio of 1/T2 of 1 bound to 3 and free 1. 1 and 2 were found to bind to 3 through the tolyl group and sulfonylurea group, respectively. The binding property of 1 was considered to be governed by the competition between the hydrophobic effect of the tolyl group and the hydrophilic effect of the sulfonylurea group in the molecule.
Tanaka
M
M
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Asahi
Y
Y
Masuda
S
S
Minagawa
K
K
D001665:Binding Sites; D003956:Dialysis; D019277:Entropy; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D019097:Spin Trapping; D014044:Tolbutamide / Q000378:metabolism*
D007004:Hypoglycemic Agents; D012709:Serum Albumin; D014044:Tolbutamide