Combinatorial Evolution of Fast-Conducting Highly Selective K+-Channels via Modularly Tunable Directional Assembly of Crown Ethers,Journal of the American Chemical Society

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Combinatorial Evolution of Fast-Conducting Highly Selective K+-Channels via Modularly Tunable Directional Assembly of Crown Ethers
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2017-08-30 00:00:00 , DOI: 10.1021/jacs.7b04335
Changliang Ren ₁ , Jie Shen ₁ , Huaqiang Zeng ₁

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We describe here a modularly tunable molecular strategy for construction and combinatorial optimization of highly efficient K⁺-selective channels. In our strategy, a highly robust supramolecular H-bonded 1D ensemble was used to order the appended crown ethers in such a way that they roughly stack on top of each other to form a channel for facilitated ion transport across the membrane. Among 15 channels that all prefer K⁺ over Na⁺ ions, channel molecule 5F8 shows the most pronounced optimum for K⁺ while disfavoring all other biologically important cations (e.g., Na⁺, Ca²⁺ and Mg²⁺). With a K⁺/Na⁺ selectivity of 9.8 and an EC₅₀ value of 6.2 μM for K⁺ ion, 5F8 is clearly among the best synthetic potassium channels developed over the past decades.

中文翻译：

通过冠醚的模块化可调方向组装，快速传导高选择性K ⁺通道的组合演化

我们在这里描述了用于高效K ^+选择通道的构建和组合优化的模块化可调分子策略。在我们的策略中，使用高度健壮的超分子H键合1D集成体来订购附加的冠醚，以使它们彼此大致堆叠以形成通道，以促进离子跨膜传输。在15个都比Na ⁺离子更喜欢K ^+的通道中，通道分子5F8显示了最明显的K ⁺最佳值，同时不利于所有其他生物学上重要的阳离子（例如Na ⁺，Ca ²⁺和Mg ²⁺）。用K ⁺ / Na⁺对K ⁺离子的选择性为9.8，EC ₅₀值为6.2μM，5F8显然是过去几十年来开发的最佳合成钾通道之一。

更新日期：2017-08-30

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