Redox‐Regulated Synthetic Channels: Enabling Reversible Ion Transport by Modulating the Ion‐Permeation Pathway

Author:

Shi Linlin1,Zhao Wen1,Jiu Zhihui1,Guo Jingjing2,Zhu Qiuhui1,Sun Yonghui1,Zhu Bo1,Chang Junbiao1,Xin Pengyang1ORCID

Affiliation:

1. State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, NMPA Key Laboratory for Research and Evaluation of Innovative Drug, School of Chemistry and Chemical Engineering Henan Normal University Xinxiang 453007 China

2. Centre in Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences Macao Polytechnic University Macao 999078 China

Abstract

AbstractNatural redox‐regulated channel proteins often utilize disulfide bonds as redox sensors for adaptive regulation of channel conformations in response to diverse physiological environments. In this study, we developed novel synthetic ion channels capable of reversibly switching their ion‐transport capabilities by incorporating multiple disulfide bonds into artificial systems. X‐ray structural analysis and electrophysiological experiments demonstrated that these disulfide‐bridged molecules possess well‐defined tubular cavities and can be efficiently inserted into lipid bilayers to form artificial ion channels. More importantly, the disulfide bonds in these molecules serve as redox‐tunable switches to regulate the formation and disruption of ion‐permeation pathways, thereby achieving a transition in the transmembrane transport process between the ON and OFF states.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Henan Province

Central Plains Scholars and Scientists Studio Fund

Publisher

Wiley

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