Nanofluidic Device for Detection of Lysine Methylpeptides and Sensing of Lysine Methylation.
Nanofluidic Device for Detection of Lysine Methylpeptides and Sensing of Lysine Methylation.
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DOI：
10.1021/acs.analchem.3c01074
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发表时间：
2023-05
影响因子：
7.4
通讯作者：
Yuting Xiong;Minmin Li;Yuchen Cao;Zan Li;Yongxin Chang;Xinjia Zhao;Guangyan Qing
中科院分区：
文献类型：
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作者：
Yuting Xiong;Minmin Li;Yuchen Cao;Zan Li;Yongxin Chang;Xinjia Zhao;Guangyan Qing
蛋白质甲基化是翻译后修饰(PTM)中最小但又极其重要的过程。蛋白质中这种微小的化学惰性添加使甲基化分析更具挑战性，因此需要一种有效的工具来识别和检测。在这里，我们提出了一种基于功能化纳米通道的纳米流体电传感器件，该通道是通过点击化学将含有单三氮唑的对磺基杯[4]芳烃(TSC)引入到单个不对称的聚合物纳米通道中而构建的。该装置可以选择性地检测具有亚微克分子灵敏度的赖氨酸甲基肽，区分不同的赖氨酸甲基化状态，并在肽水平上实时监测甲基转移酶对赖氨酸甲基化过程的影响。引入的TSC分子具有受限的不对称构型，具有与赖氨酸甲基肽选择性结合的显著能力，再加上络合铜离子的释放，使设备能够将分子水平的识别转变为纳米流体电子设备离子电流的可识别变化，从而使检测成为可能。这项工作可以作为开发一种新的甲基转移酶分析和在PTM蛋白质组学中针对赖氨酸甲基化的化学物质的垫脚石。
Protein methylation is the smallest possible yet vitally important post-translational modification (PTM). This small and chemically inert addition in proteins makes the analysis of methylation more challenging, thus calling for an efficient tool for the sake of recognition and detection. Herein, we present a nanofluidic electric sensing device based on a functionalized nanochannel that was constructed by introducing monotriazole-containing p-sulfonatocalix[4]arene (TSC) into a single asymmetric polymeric nanochannel via click chemistry. The device can selectively detect lysine methylpeptides with subpicomole sensitivity, distinguish between different lysine methylation states, and monitor the lysine methylation process by methyltransferase at the peptide level in real time. The introduced TSC molecule, with its confined asymmetric configuration, presents the remarkable ability to selectively bind to lysine methylpeptides, which, coupled with the release of the complexed Cu ions, allows the device to transform the molecular-level recognition to the discernible change in ionic current of the nanofluidic electric device, thus enabling detection. This work could serve as a stepping stone to the development of a new methyltransferase assay and the chemical that specifically targets lysine methylation in PTM proteomics.