Binding analysis of nilvadipine to plasma lipoproteins by capillary electrophoresis-frontal analysis
Binding analysis of nilvadipine to plasma lipoproteins by capillary electrophoresis-frontal analysis
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DOI：
10.1016/s0731-7085(99)00197-1
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发表时间：
1999-12-01
影响因子：
3.4
通讯作者：
El Kommos, ME
中科院分区：
文献类型：
--
作者：
Mohamed, NAL;Kuroda, Y;El Kommos, ME
将毛细管电泳联用前沿分析(HPCE/FA)用于钙通道阻滞剂尼伐地平与血浆脂蛋白对映体选择性结合的超微分析。将药物-脂蛋白混合溶液流体力学引入非涂层熔融石英毛细管中，用于毛细管电泳法。由于NV在RUN缓冲液(pH 7.4)中不带电荷，因此未结合的NV通过电渗流向阴极端移动，这比带负电的脂蛋白和结合的NV的电泳迁移速度快。一旦未结合的NV离开脂蛋白，结合的NV就会迅速从蛋白质中释放出来，以维持结合平衡。因此，NV作为具有高原地区的地带迁移。出现在电泳图上的这个平台区的NV浓度与初始样品溶液中的未结合NV浓度相同。研究发现，NV与高密度脂蛋白、低密度脂蛋白和氧化型低密度脂蛋白的结合是非特异性和非对映体选择性的。这些脂蛋白的脂类部分似乎主要发生分配样结合。NV与低密度脂蛋白的总结合亲和力约为与高密度脂蛋白的结合亲和力的7倍，低密度脂蛋白的氧化显著提高了结合亲和力。(C)1999 Elsevier Science B.V.保留所有权利。
Capillary electrophoresis coupled with frontal analysis (HPCE/FA) was applied to the ultramicro analysis of enantioselective binding of nilvadipine (NV), a calcium channel blocker, to plasma lipoproteins. The drug-lipoprotein mixed solution was hydrodynamically introduced into a non-coated fused silica capillary for capillary electrophoresis. Since NV has no electric charge in the run buffer (pH 7.4), the unbound NV moved towards the cathodic end by electroosmotic flow, which was faster than the electrophoretic migrations of negatively charged lipoproteins and the bound NV. Once unbound NV migrated apart from lipoprotein, and bound NV was quickly released from the protein to maintain the binding equilibrium. Thus, NV migrated as a zone with a plateau region. The concentration of NV in this plateau region appearing on the electrophorogram was the same as the unbound NV concentration in the initial sample solution. It was found that the binding of NV to high-density lipoprotein (HDL), low-density lipoprotein (LDL) and oxidized LDL was non-specific and not enantioselective. Partition-like binding to the lipid part of these lipoproteins seemed to occur dominantly. The total binding affinities of NV to LDL were about seven times stronger than those to HDL, and the oxidation of LDL enhanced the binding affinity significantly. (C) 1999 Elsevier Science B.V. All rights reserved.