Ionophore constructed from non-covalent assembly of a G-quadruplex and liponucleoside transports K+-ion across biological membranes

Nat Commun. 2020 Jan 24;11(1):469. doi: 10.1038/s41467-019-13834-7.

Abstract

The selective transport of ions across cell membranes, controlled by membrane proteins, is critical for a living organism. DNA-based systems have emerged as promising artificial ion transporters. However, the development of stable and selective artificial ion transporters remains a formidable task. We herein delineate the construction of an artificial ionophore using a telomeric DNA G-quadruplex (h-TELO) and a lipophilic guanosine (MG). MG stabilizes h-TELO by non-covalent interactions and, along with the lipophilic side chain, promotes the insertion of h-TELO within the hydrophobic lipid membrane. Fluorescence assays, electrophysiology measurements and molecular dynamics simulations reveal that MG/h-TELO preferentially transports K+-ions in a stimuli-responsive manner. The preferential K+-ion transport is presumably due to conformational changes of the ionophore in response to different ions. Moreover, the ionophore transports K+-ions across CHO and K-562 cell membranes. This study may serve as a design principle to generate selective DNA-based artificial transporters for therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetulus
  • G-Quadruplexes*
  • Humans
  • Ion Transport*
  • K562 Cells
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Nucleosides / chemical synthesis
  • Nucleosides / chemistry*
  • Potassium Ionophores / chemical synthesis
  • Potassium Ionophores / chemistry*
  • Spectrometry, Fluorescence

Substances

  • Lipid Bilayers
  • Nucleosides
  • Potassium Ionophores