Highly active artificial potassium channels having record-high K+/Na+ selectivity of 20.1

• Published in: Chinese chemical letters Vol. 34; no. 12; p. 108355
• Main Authors: Ma, Haowen, Ye, Ruijuan, Jin, Lei, Zhou, Shaoyuan, Ren, Changliang, Ren, Haisheng, Shen, Jie, Zeng, Huaqiang
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2023
• Subjects: Artificial membrane transporters; Artificial potassium channels; Crown ethers; Social self-sorting; Supramolecular chemistry; Transport selectivity; Artificial membrane transporters; Transport selectivity; Artificial potassium channels; Crown ethers; Social self-sorting; Supramolecular chemistry
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2023.108355

Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task. In this work, we demonstrate that a strategic application of steric code-based social self-sorting offers a novel means to enhance ion transport selectivities of artificial ion channels, alongside with boosted ion transport activities. More specifically, two types of mutually compatible sterically bulky groups (benzo-crown ether and tert‑butyl group) were appended onto a monopeptide-based scaffold, which can order the bulky groups onto the same side of a one-dimensionally aligned H-bonded structure. Strong steric repulsions among the same type of bulky groups (either benzo-crown ethers or tert‑butyl groups), which are forced into proximity by H-bonds, favor the formation of hetero-oligomeric ensembles that carry an alternative arrangement of sterically compatible benzo-crown ethers and tert‑butyl groups, rather than homo-oligomeric ensembles containing a single type of either benzo-crown ethers or tert‑butyl groups. Coupled with side chain tuning, this social self-sorting strategy delivers highly active hetero-oligomeric K+-selective ion channel (5F12‧BF12)n, displaying the highest K+/Na+ selectivity of 20.1 among artificial potassium channels and an excellent EC50 value of 0.50 µmol/L (0.62 mol% relative to lipids) in terms of single channel concentration We demonstrate here that a strategic application of steric code-based social self-sorting offers a novel means to enlarge the separation distance between the vertically aligned crown ethers while reducing the number of crown ethers that make up the transmembrane ion transport pathway. As a result, greatly enhanced ion transport selectivity and boosted ion transport activities were obtained, giving rise to record-high K+/Na+ selectivity of 20.1. [Display omitted]