MEMBRANE PARTITION-COEFFICIENTS CHROMATOGRAPHICALLY MEASURED USING IMMOBILIZED ARTIFICIAL MEMBRANE SURFACES
MEMBRANE PARTITION-COEFFICIENTS CHROMATOGRAPHICALLY MEASURED USING IMMOBILIZED ARTIFICIAL MEMBRANE SURFACES
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DOI：
10.1021/ac00100a011
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发表时间：
1995-02-15
影响因子：
7.4
通讯作者：
PIDGEON, C
中科院分区：
文献类型：
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作者：
ONG, SW;LIU, HL;PIDGEON, C
固定化人工膜（IAM）是通过共价固定细胞膜磷脂制备的色谱表面。 IAM 表面模仿流体细胞膜。在 IAM 柱上测量的溶质容量因子 (k'(IAM)) 与在流体脂质体系统中测量的溶质平衡分配系数 (K-m') 密切相关。对于 23 种结构不相关的化合物，log-(k'(IAM)) 与 log(K-m') 相关，线性相关系数 r = 0.907。这表明 IAM 键合相和水性流动相之间的溶质分配类似于脂质体和水相之间的溶质分配。尽管 IAM 层析和脂质体分配都可以用作预测溶质分配到细胞膜中的体外方法，但 IAM 层析在实验上比脂质体系统更方便。为了研究脂质结构对药物与 IAM 结合的影响，从三种不同的磷脂酰胆碱配体制备了 IAM：（i）二酰化磷脂酰胆碱配体，（ii）单链醚磷脂酰胆碱配体，和（iii）缺乏甘油主链的单链磷脂酰胆碱配体。所有这些 IAM 的溶质保留数据都是相同的，因此，溶质与液膜结合的预测也是相同的。这表明固定的磷脂酰胆碱配体的结构对于溶质的结合并不重要。由于结构并不重要，因此溶质与膜的结合是体相性质，即决定溶质结合性质的是配体产生的界面，而不是配体本身。使用辛醇/水系统的溶质分配与 k'(IAM) 不相关，除非正在评估一系列同源的疏水性溶质。
Immobilized artificial membranes (IAMs) are chromatographic surfaces prepared by covalently immobilizing cell membrane phospholipids. IAM surfaces mimic fluid cell membranes. Solute capacity factors (k'(IAM)) measured on IAM columns correlate very well with solute equilibrium partition coefficients (K-m') measured in fluid liposome systems. For 23 structurally unrelated compounds, log-(k'(IAM)) correlates with log(K-m') with a linear correlation coefficient r = 0.907. This indicates that solute partitioning between the IAM bonded phase and the aqueous mobile phase is similar to the solute partitioning between liposomes and the aqueous phase. Although both IAM chromatography and liposome partitioning can be used as in vitro methods to predict solute partitioning into cell membranes, IAM chromatography is experimentally convenient compared to liposome systems. To study the effect of lipid structure on drug binding to IAMs, IAMs were prepared from three different phosphatidylcholine ligands: (i) a diacylated phosphatidylcholine ligand, (ii) a single chain ether phosphatidylcholine ligand, and (iii) a single chain phosphatidylcholine ligand that lacks a glycerol backbone. Solute retention data were identical for all of these IAMs, and consequently, predictions of solute binding to fluid membranes were also identical. This indicates that the structure of the phosphatidylcholine ligand that is immobilized is not critical for the binding of solutes. Since the structure is not important, the binding of solutes to membranes is a bulk phase property, i.e., it is the interface created by the ligands that determines the solute binding properties, not the ligands themselves. Solute partitioning using octanol/water systems does not correlate with k'(IAM) unless a homologous series of hydrophobic solutes is being evaluated.