We report here a novel class of cation transporters with extreme simplicity, opening a whole new dimension of scientific research for finding small molecule-based cation transporters for therapeutic applications. Comprising three modular components (a headgroup, a flexible alkyl chain-derived body, and a crown ether-derived foot for ion binding), these transporters efficiently (EC₅₀ = 0.18–0.41 mol % relative to lipid) and selectively (K⁺/Na⁺ selectivity = 7.0–9.5) move K⁺ ions across the membrane. Importantly, the most active (EC₅₀ = 0.18–0.22 mol %) and highly selective series of transporters A12, B12, and C12 concurrently possess potent anticancer activities with IC₅₀ values as low as 4.35 ± 0.91 and 6.00 ± 0.13 μM toward HeLa and PC3 cells, respectively. Notably, a mere replacement of the 18-crown-6 unit in the structure with 12-crown-4 or 15-crown-5 units completely annihilates the cation-transporting ability.

中文翻译：

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基于小分子的高活性和选择性K ⁺转运蛋白，具有强大的抗癌活性

我们在此报告了一种极其简单的新型阳离子转运蛋白，为寻找用于治疗应用的基于小分子的阳离子转运蛋白开辟了一个全新的科学研究领域。这些转运蛋白由三个模块组件（一个头基，一个柔性烷基链衍生的主体和一个冠醚衍生的足用于离子键合）组成，它们的转运效率很高（相对于脂质，EC ₅₀ = 0.18-0.41 mol％），选择性地转运（K ⁺ / Na ⁺选择性= 7.0–9.5）使K ⁺离子穿过膜。重要的是，最活跃的（EC ₅₀ = 0.18–0.22 mol％）和高度选择性的一系列转运蛋白A12，B12和C12同时具有有效的IC ₅₀抗癌活性对于HeLa和PC3细胞，其值分别低至4.35±0.91和6.00±0.13μM。值得注意的是，仅将结构中的18冠6单元替换为12冠4或15冠5单元即可完全消除阳离子传输能力。