Abstract

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

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