Hybrid Pyridine–Pyridone Foldamer Channels as M2‐Like Artificial Proton Channels

Hybrid Pyridine–Pyridone Foldamer Channels as M2‐Like Artificial Proton Channels
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混合吡啶 - 吡啶酮折叠体通道为 M2 - 类似于人工质子通道

DOI:
10.1002/anie.202200259
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发表时间:
2022
期刊:
Angewandte Chemie International Edition
影响因子:
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通讯作者:
Zeng, Huaqiang
Zeng, Huaqiang
中科院分区:
--
文献类型:
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作者:
Shen, Jie;Ye, Ruijuan;Liu, Zhiwei;Zeng, Huaqiang

文献摘要

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目前,同时再现天然蛋白质通道的高选择性和高渗透率的完全非生物通道系统很少见。在这里,我们提供了一个这样的仿生通道系统,即一种新型的螺旋折叠混合酰胺折叠体家族,它可以作为强大的人造质子通道来模拟异常选择性的 Matrix-2 (M2) 质子通道的关键传输特征。这些低透水性人工通道具有直径为 3 Å 的埃级管状孔隙,传输质子的速度分别是短杆菌肽 A 和 M2 通道的 1.22 倍和 11 倍,对 Cl−、Na+ 和 K+ 离子的选择性因子极高,分别为 167.6、122.7 和 81.5。基于实验和计算结果,我们提出了一种新颖的质子传输机制,其中质子可以从两个或多个短水链创建跨通道水链,以通过 Grotthuss 机制促进其自身的跨膜通量。
Currently, completely abiotic channel systems that concurrently reproduce the high selectivity and high permeation rate of natural protein channels are rare. Here, we provide one such biomimetic channel system, i.e., a novel family of helically folded hybrid amide foldamers that can serve as powerful artificial proton channels to mimic key transport features of the exceptionally selective Matrix‐2 (M2) proton channels. Possessing an angstrom‐scale tubular pore 3 Å in diameter, these low water permeability artificial channels transport protons at a rate 1.22 and 11 times as fast as gramicidin A and M2 channels, respectively, with exceptionally high selectivity factors of 167.6, 122.7, and 81.5 over Cl−, Na+, and K+ions. Based on the experimental and computational findings, we propose a novel proton transport mechanism where a proton may create a channel‐spanning water chain from two or more short water chains to facilitate its own transmembrane flux via the Grotthuss mechanism.