赖氨酸
化学
甲基化
甲基转移酶
分子
组合化学
肽
纳米技术
离子
生物物理学
生物化学
DNA
氨基酸
有机化学
材料科学
生物
作者
Yüting Xiong,Minmin Li,Yuchen Cao,Zan Li,Yongxin Chang,Xinjia Zhao,Guangyan Qing
标识
DOI:10.1021/acs.analchem.3c01074
摘要
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.
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