State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
J Am Chem Soc. 2021 Mar 10;143(9):3284-3288. doi: 10.1021/jacs.0c12128. Epub 2021 Mar 1.
Small molecules that independently perform natural channel-like functions show greatly potential in the treatment of human diseases. Taking advantage of aromatic helical scaffolds, we develop a kind of foldamer-based ion channels with lumen size varying from 3.8 to 2.3 Å through a sequence substitution strategy. Our results clearly elucidate the importance of channel size in ion transport selectivity in molecular detail, eventually leading to the discoveries of the best artificial K channel by far and a rare sodium-preferential channel as well. High K selectivity and transport activity together make foldamers promising in therapeutic applications.
小分子独立地执行类似天然通道的功能,在治疗人类疾病方面具有巨大的潜力。利用芳香螺旋支架,我们通过序列替换策略开发了一种具有从 3.8 到 2.3 Å 不等腔径的折叠体离子通道。我们的结果从分子细节上清楚地阐明了通道大小在离子传输选择性中的重要性,最终发现了迄今为止最好的人工钾通道和一种罕见的钠偏好通道。高钾选择性和转运活性使折叠体在治疗应用中具有广阔的前景。