title: Peptides as tight junction modulators.
abstract: The first step in drug absorption is the passage of drug molecules across epithelial cell sheets. Epithelial cell sheets are pivotal for the maintenance of homeostasis in the body by acting as a biological barrier that separates the inside of the body from the outside environment. Intercellular space between the adjacent epithelial cells is tightly sealed by tight junctions (TJs), which prevent solutes from freely moving across the epithelial cell sheets. Modulation of the TJ barrier has been a potent strategy for drug absorption. Absorption enhancers have been investigated since the 1980s, and sodium caprate is clinically used as an absorption enhancer. However, the biochemical constituents and structures of TJs were not elucidated until 1993. Occludin, a tetra-transmembrane protein, was identified to be a structural component of TJs in 1993. Claudin, another tetra-transmembrane protein, was identified as a structural and functional component of TJs in 1998. Modulation of occludin- or claudin-barrier is novel methods to enhance drug absorption. Recently, synthetic TJ-binding peptides, a kinase of claudin and peptide fragments of toxins have been developed. In the present review, we summarize the recent progress in TJ-modulating peptides and discuss their potencies.
authors: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors: Azusa
authors: A
authors: Takahashi
authors: Masuo
authors: M
authors: Kondoh
authors: Miki
authors: M
authors: Kodaka
authors: Kiyohito
authors: K
authors: Yagi
mesh_terms: D000042:Absorption; D000818:Animals; D057167:Claudins / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010455:Peptides / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
chemical_list: D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010455:Peptides