Xin Pengyang, Jiu Zhihui, Shi Linlin, Shu Yuqing, Song Yufei, Sun Yonghui
State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, NMPA Key Laboratory for Research and Evaluation of Innovative Drug, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, China.
Chembiochem. 2025 Jan 2;26(1):e202400789. doi: 10.1002/cbic.202400789. Epub 2024 Nov 9.
In this study, we have successfully synthesized bis (cholesterol-dibenzo-18-crown-6-ether)-pillar[5]arene compound 1 through a click reaction, which could spontaneously insert into lipid bilayers to form ion channel due to the membrane anchor cholesterol group and show significant transport activity of K superior to Na, with a permeability ratio of K/Na equal to 4.58. Compound 1 two crown ether modules act as selective filters similar to natural K channel, which are determined to 1 : 2 binding stoichiometry to K by Job's plot and NMR titration. This structurally unambiguously unimolecule artificial channel provides ideas for constructing highly K/Na selective molecular filters.
在本研究中，我们通过点击反应成功合成了双（胆固醇 - 二苯并 - 18 - 冠 - 6 - 醚）柱[5]芳烃化合物1，由于膜锚定胆固醇基团，该化合物可自发插入脂质双层形成离子通道，并表现出显著的K转运活性优于Na，K/Na渗透率比为4.58。化合物1的两个冠醚模块充当类似于天然K通道的选择性过滤器，通过Job曲线和NMR滴定确定其与K的结合化学计量比为1∶2。这种结构明确的单分子人工通道为构建高K/Na选择性分子过滤器提供了思路。
