Synthetic anion channels: achieving precise mimicry of the ion permeation pathway of CFTR in an artificial system

Chem Sci. 2024 Nov 25. doi: 10.1039/d4sc06893a. Online ahead of print.

Abstract

CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), a naturally occurring anion channel essential for numerous biological processes, possesses a positively charged ion conduction pathway within its transmembrane domain, which serves as the core module for promoting the movement of anions across cell membranes. In this study, we developed novel artificial anion channels by rebuilding the positively charged ion permeation pathway of the CFTR in artificial systems. These synthetic molecules can be efficiently inserted into lipid bilayers to form artificial ion channels, which exhibit a preference for anions during the transmembrane transport process. More importantly, the positively charged amino acid residues located in the ion permeation pathway of these artificial channels can promote the transmembrane transport of anions through electrostatic interactions, which is consistent with the mechanism of anion transmembrane transport achieved by CFTR.