School of Chemistry and Molecular Engineering, Engineering Research Center of Nanophotonics and Advanced Instrument, Ministry of Education, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, People's Republic of China.
School of Chemistry and Molecular Engineering, Engineering Research Center of Nanophotonics and Advanced Instrument, Ministry of Education, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, People's Republic of China; School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, 226001, People's Republic of China.
Anal Chim Acta. 2021 Dec 15;1188:339167. doi: 10.1016/j.aca.2021.339167. Epub 2021 Oct 12.
ATP-sensitive potassium (K) channels couple intracellular metabolism to the electrical activity by regulating K flux across the plasma membrane, thus playing an important role in both normal and pathophysiology. To understand the mechanism of ATP regulating biological ion channels, developing an ATP-responsive artificial nanochannel is an appealing but challenging topic because K channel is a heteromultimer of two subunits (potassium channel subunit (Kir6.x) and sulfonylurea receptor (SUR)) and exhibit dynamic functions with adjustability and reversibility. Inspired by the structure of K channels, we designed a smart copolymer modified nanochannel that may address the challenge. In the tricomponent poly(N-isopropylacrylamide) (PNIPAAm, PNI)-based copolymer system, phenylthiourea was used to bind the phosphate units of nucleotides and phenylboronic acid was introduced to combine the pentose ring of the nucleoside unit. Besides, a -COOH group with electron-withdrawing property was added into the phenylthiourea units, which may promote the hydrogen-bond-donating ability of thiourea. Specially, the smart copolymer not only provided static binding sites for recognition but also translated the recognition of ATP into their dynamic conformational transitions by changing the hydrogen-bonding environments surrounding PNIPAAm chains, thus achieving the gating function of nanochannel, which resembled the integration and coordination of Kir6.x and SUR units in active K. The ATP-regulated ion channel exhibited excellent stability and reversibility. This study is the first example showing how to learn from nature to assemble the ATP-responsive artificial nanochannel and demonstrate the possible mechanism of ATP gating.
三磷酸腺苷（ATP）敏感性钾（K）通道通过调节跨质膜的 K 流来将细胞内代谢与电活动偶联，因此在正常和病理生理学中都发挥着重要作用。为了理解 ATP 调节生物离子通道的机制，开发对 ATP 有响应的人工纳米通道是一个很有吸引力但具有挑战性的课题，因为 K 通道是由两个亚基（钾通道亚基（Kir6.x）和磺酰脲受体（SUR））组成的异源多聚体，并且具有可调节性和可逆性的动态功能。受 K 通道结构的启发，我们设计了一种智能共聚物修饰的纳米通道，可能会解决这一挑战。在三组分聚（N-异丙基丙烯酰胺）（PNIPAAm，PNI）基共聚物体系中，苯硫脲用于结合核苷酸的磷酸单元，苯硼酸用于结合核苷单元的戊糖环。此外，在苯硫脲单元中引入了一个具有吸电子性质的-COOH 基团，这可能会增强硫脲的供氢键能力。特别地，智能共聚物不仅提供了用于识别的静态结合位点，而且通过改变 PNIPAAm 链周围氢键环境的变化，将 ATP 的识别转化为其动态构象转变，从而实现纳米通道的门控功能，这类似于活性 K 中 Kir6.x 和 SUR 单元的整合和协调。该受 ATP 调节的离子通道表现出优异的稳定性和可逆性。本研究首次展示了如何从自然界中学习组装对 ATP 有响应的人工纳米通道，并展示了 ATP 门控的可能机制。
