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Open AccessReview

Potential for Tight Junction Protein–Directed Drug Development Using Claudin Binders and Angubindin-1

1
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan
2
Institute of Clinical Physiology, Charité–Universitätsmedizin Berlin, 12203 Berlin, Germany
3
Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085, Japan
4
International Research and Development Center for Mucosal Vaccines, The Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan
5
Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
6
Graduate School of Medicine and Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4016; https://doi.org/10.3390/ijms20164016
Received: 24 July 2019 / Revised: 14 August 2019 / Accepted: 14 August 2019 / Published: 17 August 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
The tight junction (TJ) is an intercellular sealing component found in epithelial and endothelial tissues that regulates the passage of solutes across the paracellular space. Research examining the biology of TJs has revealed that they are complex biochemical structures constructed from a range of proteins including claudins, occludin, tricellulin, angulins and junctional adhesion molecules. The transient disruption of the barrier function of TJs to open the paracellular space is one means of enhancing mucosal and transdermal drug absorption and to deliver drugs across the blood–brain barrier. However, the disruption of TJs can also open the paracellular space to harmful xenobiotics and pathogens. To address this issue, the strategies targeting TJ proteins have been developed to loosen TJs in a size- or tissue-dependent manner rather than to disrupt them. As several TJ proteins are overexpressed in malignant tumors and in the inflamed intestinal tract, and are present in cells and epithelia conjoined with the mucosa-associated lymphoid immune tissue, these TJ-protein-targeted strategies may also provide platforms for the development of novel therapies and vaccines. Here, this paper reviews two TJ-protein-targeted technologies, claudin binders and an angulin binder, and their applications in drug development. View Full-Text
Keywords: tight junction; claudin; angulin; drug development; angubindin-1; Clostridium perfringens enterotoxin; Clostridium perfringens iota-toxin; antibody tight junction; claudin; angulin; drug development; angubindin-1; Clostridium perfringens enterotoxin; Clostridium perfringens iota-toxin; antibody
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Hashimoto, Y.; Tachibana, K.; Krug, S.M.; Kunisawa, J.; Fromm, M.; Kondoh, M. Potential for Tight Junction Protein–Directed Drug Development Using Claudin Binders and Angubindin-1. Int. J. Mol. Sci. 2019, 20, 4016.

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