Relationships between structure and high-throughput screening permeability of peptide derivatives and related compounds with artificial membranes: application to prediction of Caco-2 cell permeability

被引：53

作者：

Ano, R ^{[1
]}

Kimura, Y ^{[1
]}

Shima, M ^{[1
]}

Matsuno, R ^{[1
]}

Ueno, T ^{[1
]}

Akamatsu, M ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Agr, Kyoto 6068502, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 01期

关键词：

PAMPA; artificial membrane; Caco-2; structure permeability relationships; dipeptide derivatives; indole compounds;

D O I：

10.1016/j.bmc.2003.10.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：257 / 264

页数：8

共 43 条

[1] HYDROPHOBICITY OF DIPEPTIDES AND TRIPEPTIDES HAVING UNIONIZABLE SIDE-CHAINS AND CORRELATION WITH SUBSTITUENT AND STRUCTURAL PARAMETERS [J].