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

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 ensem-bles 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 ac-tive hetero-oligomeric K +-selective ion channel (5F12 center dot BF12)n, displaying the highest K + /Na + selectivity of 20.1 among artificial potassium channels and an excellent EC50 value of 0.50 mu mol/L (0.62 mol% relative to lipids) in terms of single channel concentration (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.