Study of Ion-Ion Interaction for Protein-Drug Binding using a Newly Developed Guanidino-Bonded Phase in Liquid Chromatography

Study of Ion-Ion Interaction for Protein-Drug Binding using a Newly Developed Guanidino-Bonded Phase in Liquid Chromatography
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使用新开发的胍基键合相在液相色谱中研究蛋白质-药物结合的离子-离子相互作用

DOI:
10.1080/10826079808003451
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发表时间:
1998
影响因子:
1.3
通讯作者:
T. Kinoshita
T. Kinoshita
中科院分区:
化学4区
文献类型:
--
作者:
Rie Miyakaki;T. Hanai;J. Suzuki;T. Kinoshita

文献摘要

被引文献

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摘要研究了胍基液相色谱对酸性药物的色谱行为。季阴离子交换基团,即,胍基作为弱阴离子交换剂,色谱保留容量与DEAE离子交换剂相似。在pH 7.4的50 mM磷酸钠缓冲液中,酸性药物在胍基相中保留较差。这一发现解释了为什么药物-蛋白质结合常数通常与药物的疏水性有关,以及为什么离子-离子相互作用似乎对分子相互作用没有贡献。保留机制的计算化学分析表明,静电力主要有助于药物在胍基相的保留。
Abstract The chromatographic behavior of acidic drugs was studied using a guanidino phase in liquid chromatography. The quaternary anion-exchange group, i.e., the guanidino group, acted as a weak anion exchanger and the chromatographic retention capacity was similar to that of a DEAE ion exchanger. Acidic drugs were poorly retained on guanidino phase in a 50mM sodium phosphate buffer at pH7.4. This finding explains why drug-protein binding constants are generally related to the hydrophobicity of drugs and why the ion-ion interaction has seemed not to contribute to the molecular interaction. The computational chemical analysis of the retention mechanism indicated that mainly electrostatic force contributes to the retention of drugs on the guanidino phase.