Nghiên cứu về Angubindin-1

Trích từ : Angubindin-1, a novel paracellular absorption enhancer acting at the tricellular tight junction. ( DOI :10.1016/j.jconrel.2017.05.024 )

A limiting barrier for mucosal absorption of drugs is the tight junction (TJ). TJs exist between two adjacent cells (bicellular TJ, bTJ) and at the sites where three cells meet (tricellular TJ, tTJ). We present a novel approach which employs a physiologically regulated pathway for the passage of large molecules through the tTJ. Main barrier-relevant tTJ proteins are tricellulin and angulin-1 to -3. We developed an angulin binder from Clostridium perfringens iota-toxin (Ib) whose receptor is angulin-1. An Ib fragment corresponding to amino acids 421-664 (Ib421-664) of iota-toxin proved to bind in cells expressing angulin-1 and -3, but not angulin-2. This binding led to removal of angulin-1 and tricellulin from the tTJ which enhanced the permeation of macromolecular solutes. Ib421-664 enhanced intestinal absorption in rats and mice. Our findings indicate that Ib421-664, which we designate angubindin-1, is a modulator of the tTJ barrier and that modulation of that barrier qualifies for a new strategy of developing a mucosal absorption enhancer.

Tìm (Ib421-664)  sẽ ra tiếp : Binding and Internalization of Clostridium perfringens Iota-Toxin in Lipid Rafts  xuất bản năm 2004 :


Trong bài Angubindin-1 opens the blood–brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system :

Cũng nhắc tới: The plasmid encoding angubindin-1 (pGEX-Ib421–664) was expressed as a fusion protein with glutathione S-transferase (GST) in Escherichia coli strain BL21 (DE3), as described previously [21