STOPPED-FLOW STUDIES ON DRUG-PROTEIN BINDING .1. KINETICS OF WARFARIN-BINDING TO HUMAN-SERUM ALBUMIN
STOPPED-FLOW STUDIES ON DRUG-PROTEIN BINDING .1. KINETICS OF WARFARIN-BINDING TO HUMAN-SERUM ALBUMIN
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DOI：
10.1007/bf00505744
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发表时间：
1980-01-01
影响因子：
3.6
通讯作者：
LASSMANN, A
中科院分区：
文献类型：
--
作者：
RIETBROCK, N;LASSMANN, A
采用停流法研究了华法林与人血清白蛋白（HSA）的结合。 37度。 C 稳定华法林-HSA 复合物解离速度的速率常数为 10 秒（t1/2 [半衰期] = 0.07 秒）。测量了华法林与 HSA 结合的浓度和温度依赖性缔合常数（6°C 时为 2.5°Cntdot.105/M 每秒，22°C 时为 9.8°Cntdot.105/M 每秒，以及 37°C 时为 15.3°Cntdot.105/M 每秒）。我们通过实验获得的弛豫常数最好的解释是 HSA 分子上存在 5 个等效的华法林低亲和力结合位点，每个位点都能够转化为高亲和力位点。测得的该转化的活化能为 57.5 KJ/M。
The binding of warfarin to human serum albumin (HSA) with the stopped-flow method was studied. At 37.degree. C the rate constant for the velocity of dissociation of the stable warfarin-HSA complex is 10 s (t1/2 [half-life] = 0.07 s). Concentration and temperature-dependent association constants for warfarin binding to HSA were measured (2.5 .cntdot. 105/M per s at 6.degree. C, 9.8 .cntdot. 105/M per s at 22.degree. C and 15.3 .cntdot. 105/M per s at 37.degree. C). Our experimentally obtained relaxation constants are best explained by the existence of 5 equivalent low affinity binding sites for warfarin on the HSA molecule, each capable of conversion into a high affinity site. The measured activation energy for this conversion is 57.5 KJ/M.