Wilting J, van der Giesen W F, Janssen L H, Weideman M M, Otagiri M, Perrin J H
J Biol Chem. 1980 Apr 10;255(7):3032-7.
The pH dependence of the binding of warfarin to human serum albumin has been studies by circular dichroism, fluorescence, and equilibrium dialysis. The pH dependences of the induced ellipticity and the fluorescent intensity of the warfarin . albumin complexes at low drug to protein ratios parallel the neutral to base transition, occurring in the protein over the pH range 6 to 9. Dialysis data show albumin to have a single high affinity site for warfarin over this pH range. This affinity is higher for the basic than for the neutral conformation. Calcium ions increase the high affinity constant of warfarin for albumin over the same pH region, by affecting the neutral to base transition. On the other hand, chloride ions reduce the induced ellipticity and the fluorescent intensity of the complexes at all pH investigated, the mechanism being primarily that of displacement of the drug from albumin.
通过圆二色性、荧光和平衡透析研究了华法林与人血清白蛋白结合的pH依赖性。在低药物与蛋白质比例下，华法林-白蛋白复合物的诱导椭圆率和荧光强度的pH依赖性与蛋白质在pH 6至9范围内发生的中性到碱性转变平行。透析数据表明，在该pH范围内白蛋白对华法林有一个单一的高亲和力位点。这种亲和力对于碱性构象比对中性构象更高。钙离子通过影响中性到碱性转变，在相同pH区域增加了华法林对白蛋白的高亲和力常数。另一方面，氯离子在所有研究的pH下都降低了复合物的诱导椭圆率和荧光强度，其机制主要是药物从白蛋白上的置换。
