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

Rieko Ano, Yukitaka Kimura, Machiko Urakami, Motohiro Shima, Ryuichi Matsuno, Tamio Ueno, Miki Akamatsu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)249-255
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 2 2004
Externally publishedYes

Keywords

  • Caco-2
  • Dipeptide derivatives
  • Indole compounds
  • Structure-permeability relationships

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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