A DNA-Inspired Synthetic Ion Channel Based on G–C Base Pairing

Abstract

A dinucleoside containing guanosine and cytidine at the end groups has been prepared using a modular one-pot azide-alkyne cycloaddition. Single channel analysis showed that this dinucleoside predominantly forms large channels with 2.9 nS conductance for the transport of potassium ions across a phospholipid bilayer. Transmission electron microscopy, atomic force microscopy, and circular dichroism spectroscopy studies reveal that this dinucleoside can spontaneously associate through Watson-Crick canonical H-bonding and π-π stacking to form stable supramolecular nanostructures. Most importantly, the ion channel activity of this G-C dinucleoside can be inhibited using the nucleobase cytosine.

Construction of a cross-layer linked G-octamer via conformational control: a stable G-quadruplex in H-bond competitive solvents

“…Inspired by this unique H-bond assembly, researchers have been devoted to developing guanine derivatives to achieve controllable G-quadruplex formation from small molecules 21–23. Some interesting applications have been identified with various G-quartet assemblies, including lipophilic ion channels,24–26 supramolecular hydrogels,27–29 nanomaterials,30,31 potential targets for cancer therapy,32,33 and more 34–37. Although many examples of G-quartet formation through various modified guanine derivatives have been reported, studies on controlling G-quartet stacking molecularity are relatively rare 38,39.…”

Biomimetische DNA‐Nanoröhren: Gezielte Synthese und Anwendung nanoskopischer Kanäle

“…Dash et al. berichteten über einen einfachen Ionenkanal aus G‐C‐Dinukleotidstapeln mit einer Leitfähigkeit von 2.9 nS für den Transport von Kaliumionen …”

A Novel Cyclic Mobile Transporter Can Induce Apoptosis by Facilitating Chloride Anion Transport into Cells

“…Cellular ion transport systems play crucial roles in different biological processes. 1 − 5 Malfunctions of endogenous ion channels are responsible for multiple disease conditions, including cystic fibrosis, 5 − 7 Bartter’s syndrome, 8 myotonia, 9 epilepsy, 10 Gitelman syndrome, 11 Dent’s disease, 12 renal tubular acidosis, 13 deafness, 14 several neurological disorders, and cancer. 15 − 18 Artificial channel replacement therapy 19 has been introduced recently for the treatment of the diseases associated with ion channel dysfunctions, in which synthetic anion transporters 18 , 20 − 31 are used to replace endogenous malfunctioning ion channels.…”