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

Angew Chem Int Ed Engl. 2024 May 13;63(20):e202403667. doi: 10.1002/anie.202403667. Epub 2024 Mar 15.

Abstract

Natural 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.

Keywords: Cyclodextrins; Disulfide Bonds; Ion Channels; Supramolecular Chemistry; Transmembrane Transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Disulfides* / chemistry
  • Ion Channels* / chemistry
  • Ion Channels* / metabolism
  • Ion Transport*
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Models, Molecular
  • Oxidation-Reduction*

Substances

  • Disulfides
  • Ion Channels
  • Lipid Bilayers