Ano Rieko, Kimura Yukitaka, Shima Motohiro, Matsuno Ryuichi, Ueno Tamio, Akamatsu Miki
Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Bioorg Med Chem. 2004 Jan 2;12(1):257-64. doi: 10.1016/j.bmc.2003.10.002.
To evaluate absorption of compounds across the membrane via a transcellular route, the permeability of peptide derivatives and related compounds was measured by the parallel artificial membrane permeation assay (PAMPA). The permeability coefficients by PAMPA were analyzed quantitatively using classical QSAR and Volsurf approaches with the physicochemical parameters. The results from both approaches showed that hydrogen bonding ability of molecules in addition to hydrophobicity at a particular pH were significant in determining variations in PAMPA permeability coefficients. The relationship between Caco-2 cell permeability and artificial lipid membrane permeability was then determined. The compounds were sorted according to their absorption pathway in the plot of the Caco-2 cell and PAMPA permeability coefficients.
为了评估化合物通过跨细胞途径穿过膜的吸收情况，采用平行人工膜渗透试验（PAMPA）测定了肽衍生物及相关化合物的渗透性。利用经典的定量构效关系（QSAR）和Volsurf方法结合物理化学参数对PAMPA的渗透系数进行了定量分析。两种方法的结果均表明，在特定pH值下，除疏水性外，分子的氢键结合能力对PAMPA渗透系数的变化具有重要影响。随后确定了Caco-2细胞渗透性与人工脂质膜渗透性之间的关系。根据Caco-2细胞和PAMPA渗透系数的关系图，对化合物的吸收途径进行了分类。
