A highly active anion-selective aminocyclodextrin ion channel
A highly active anion-selective aminocyclodextrin ion channel
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DOI：
10.1002/anie.200501625
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Gin, MS
中科院分区：
文献类型：
--
作者：
Madhavan, N;Robert, EC;Gin, MS
离子通道蛋白是自然界中发现的介导带电物质跨细胞膜转运的分子装置。人体的各种功能，如神经和肌肉兴奋、激素分泌、细胞增殖和体内平衡，都受到离子通道的调节。[1]在自然界中的离子转运机制的有效运作，导致了相当大的兴趣，了解这些蛋白质介导的选择性，调节跨膜离子转运的机制。[2]此外，离子通道在盐水条件下影响电信号的能力激发了它们作为生物传感器，[3]治疗剂[4]和其他有用材料的用途。[5]尽管受控离子转运具有潜在的实用性，但蛋白质在体外的相对不稳定性可能会阻止其在商业应用中的使用。在合成更强大的人工通道的进展提供了一个可行的解决方案的离子通道的稳定性问题，从而使仿生信号组件的建设。决定离子通道生理功能的一个重要特征是离子选择性。离子通道可以根据离子通过通道孔的渗透性差异分为阳离子选择性通道和阴离子选择性通道。离子通道对阳离子的选择性已经被广泛研究，并且使用β-环糊精，[6]冠醚，[7]肽，[8]和杯芳烃[9]的几种合成类似物是迄今为止已经开发的分子支架。相比之下，对于阴离子而不是阳离子具有选择性的合成通道的实例少得多。Gokel [10]和Matile [11]开发的肽合成通道和Regen [12]开发的甾醇模拟物已被证明在磷脂膜内自组装时优先转运阴离子而不是阳离子。本文报道了一种高活性的单体环糊精基离子通道（1，图1），它不仅对阴离子的选择性优于阳离子，而且还能区分卤阴离子（I_x> Br_x> Cl_x）。
Ion-channel proteins are molecular devices found in nature that mediate the transport of charged species across cell membranes. Various functions in the human body, such as nerve and muscle excitation, hormonal secretion, cell proliferation, and homeostasis, are regulated by ion channels.[1] The efficient functioning of ion-transport machinery in nature has led to considerable interest in understanding the mechanisms by which these proteins mediate selective, regulated transmembrane ion transport.[2] Furthermore, the ability of ion channels to effect electrical signaling under aqueous saline conditions has inspired their use as biosensors,[3] therapeutic agents,[4] and other useful materials.[5] Despite the potential utility of controlled ion transport, the relative instability of proteins in vitro will likely prohibit their use in commercial applications. Advances in the synthesis of more robust artificial channels provide a viable solution to the problem of ion-channel stability, thus enabling the construction of biomimetic signaling components. An important feature that dictates the physiological function of ion channels is ion selectivity. Ion channels can be classified as cation or anion selective on the basis of the differential permeability of ions through the channel pore. Ion channels selective for cations over anions have been widely studied, and several synthetic analogues that use β-cyclodextrin,[6] crown ethers,[7] peptides,[8] and calixarenes [9] are among the molecular scaffolds that have been developed to date. In contrast, there have been far fewer examples of synthetic channels that are selective for anions over cations. Peptidic synthetic channels developed by Gokel [10] andMatile [11] and sterol mimics developed by Regen [12] have been shown to preferentially transport anions over cations upon self-assembly within phospholipid membranes. Reported herein is a highly active, monomeric cyclodextrinbased ion channel (1, Figure1) that displays not only selectivity for anions over cations but also discriminates among halide anions (IÀ> BrÀ> ClÀ).