Pharmaceutical research · 1996
Mode of interaction of loop diuretics with human serum albumin and characterization of binding site.
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Takamura N, Haruta A, Kodama H, Tsuruoka M, Yamasaki K, Suenaga A, Otagiri M
Аннотация
PURPOSE: The purpose of this study was to investigate the binding mechanism of loop diuretics with HSA and to characterize the binding site on HSA.
METHODS: Quantitative analysis of potential interaction between ligands bound to HSA was performed by equilibrium dialysis and data for binding of the two ligands to HSA were analyzed on the basis of a theoretical model of simultaneous binding of two ligands.
RESULTS: The binding of loop diuretics is dependent upon the N-B transition, conformational change of albumin. Furthermore, from the results of binding of the drugs to modified HSA, the lysine residue seems to be involved in the binding of loop diuretics to HSA.
CONCLUSIONS: Analysis using models describing independent, competitive, cooperative and anti-cooperative binding led to the conclusion that loop diuretics bind to site I, particularly to the warfarin region on HSA.
METHODS: Quantitative analysis of potential interaction between ligands bound to HSA was performed by equilibrium dialysis and data for binding of the two ligands to HSA were analyzed on the basis of a theoretical model of simultaneous binding of two ligands.
RESULTS: The binding of loop diuretics is dependent upon the N-B transition, conformational change of albumin. Furthermore, from the results of binding of the drugs to modified HSA, the lysine residue seems to be involved in the binding of loop diuretics to HSA.
CONCLUSIONS: Analysis using models describing independent, competitive, cooperative and anti-cooperative binding led to the conclusion that loop diuretics bind to site I, particularly to the warfarin region on HSA.