Relationship between structure and permeability of dipeptide derivatives containing tryptophan and related compounds across human intestinal epithelial (Caco-2) cells

被引：17

作者：

Ano, R ^{[1
]}

Kimura, Y ^{[1
]}

Urakami, M ^{[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：

Caco-2; structure-permeability relationships; dipeptide derivatives; indole compounds;

D O I：

10.1016/j.bmc.2003.10.001

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：

The permeability of dipeptide derivatives containing tryptophans and indole derivatives through Caco-2 cells was used as an in vitro intestinal absorption model in order to clarify structural factors which influence their intestinal epithelial permeation and metabolism. Most peptide derivatives were hydrolysed not only by the cytosolic enzymes in Caco-2 cells during permeation but also by enzymes released to the apical. solution before cell permeation. The N-terminal blocked dipeptides were more resistant to hydrolases expressed in the Caco-2 cells and indole derivatives were not entirely degraded. Based on compound concentration dependency and comparison of permeability coefficients in apical-to-basolateral and basolateral-to-apical directions, the main absorption mechanism of compounds were determined. Compounds were then classified into three groups; (1) passively transported compounds, (2) actively transported compounds and (3) compounds excreted by P-glycoprotein. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：249 / 255

页数：7

共 28 条

[1] QUANTITATIVE APPROACHES TO DELINEATE PARACELLULAR DIFFUSION IN CULTURED EPITHELIAL-CELL MONOLAYERS [J].