Highly Selective Artificial Potassium Ion Channels Constructed from Pore‐Containing Helical Oligomers

Abstract

Potassium ion channels specifically transport K + ions over Na + ions across ac ell membrane.Aqueue of four binding sites in the K + channel pore playss ignificant roles during highly selective conduction. Akind of aromatic helical oligomer was synthesized that can selectively bind K + over Na + .B ya romatic stackingo fh elical oligomers,atype of artificial K + channelsw ith contiguous K + binding sites was constructed. Such artificial channelse xhibited exceptionally high K + /Na + selectivity ratios during transmembrane ion conduction.Potassium channels transport K + ions across the cell membrane,w hich is av ital process in living systems and is involved in many physiological activities,s uch as neural signaling and maintenance of cellular homeostasis. [1] It is wellknown that K + channels possess ahighly conserved signature sequence (TVGYG), which structurally forms as electivity filter. Presence of four K + ion binding sites in the selectivity filter endows K + channels with extraordinary selectivity for K + ions over slightly smaller Na + ions. [2] Moreover,t he K + channel pore comprising of four binding sites plays akey role for high K + conduction rate.A lthough the atomic structures of some K + channels have deciphered the mystery of selective K + ion conduction by X-ray crystallographic studies, [2,3] it remains challenging to structurally and functionally mimic K + channels.S tudy of highly selective artificial K + channels not only could chemically provide evidences on the understanding of the selectivity conduction mechanism of natural ion channels, [4,5] but also might lead to potential applications in various areas including sensors,s eparation and therapeutic technologies. [6] Artificial ion channels possessing highly selective transport ability are particularly difficult to make at present, [7] despite the conduction specificity of natural ion channels being routinely common. Recently,w ed iscovered that the helical codon 2,5-bis(2-pyridyl)-1,3,4-oxadiazole could be imbedded into ar igid polymeric chain, giving rise to the formation of helically folded pore-containing macromole-cules. [8] Thep ore-containing helical macromolecules showed preferential cation conduction in biomimetic transmembrane channel systems.T his observation inspired us to optimize the pore structure of helical channels to develop highly selective artificial ion channels.Previous studies suggested that aqueue of contiguous ion binding sites in the channel pore plays significant roles in highly selective conduction of channel models. [9] Therefore,w ew onder if as ynthetic channel pore containing multiple ion binding sites can show the transporting specificity,a sn atural K + channels do.H erein, we synthesized ak ind of aromatic helical oligomers that can selectively bind K + over Na + .Byaromatic stacking of helical oligomers,atype of artificial K + channels with contiguous K + binding sites was constructed. Surprisingly,wediscovered that such artificial channels exhibited high K + /Na + selectivity ratios during transmemb...

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Small Molecule-Based Highly Active and Selective K+ Transporters with Potent Anticancer Activities

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Biomimetic Separation of Transport and Matrix Functions in Lamellar Block Copolymer Channel-Based Membranes

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