Potential for Tight Junction Protein-Directed Drug Development Using Claudin Binders and Angubindin-1.
Clostridium perfringens enterotoxin
Clostridium perfringens iota-toxin
angubindin-1
angulin
antibody
claudin
drug development
tight junction
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
17 Aug 2019
17 Aug 2019
Historique:
received:
24
07
2019
revised:
14
08
2019
accepted:
14
08
2019
entrez:
21
8
2019
pubmed:
21
8
2019
medline:
6
2
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31426497
pii: ijms20164016
doi: 10.3390/ijms20164016
pmc: PMC6719960
pii:
doi:
Substances chimiques
Claudins
0
Tight Junction Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan
ID : 19H04468, 18K19400, 18H03190, 16K13044, and 24390042
Organisme : grants from the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) of AMED
ID : JP19am0101077, JP19am0101084, JP19am0101090
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