Universal Strategy to Develop Fluorogenic Probes for Lysine Deacylase/Demethylase Activity and Application in Discriminating Demethylation States
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Pages (from-to) | 28-39 |
Journal / Publication | ACS Sensors |
Volume | 8 |
Issue number | 1 |
Online published | 5 Jan 2023 |
Publication status | Published - 27 Jan 2023 |
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DOI | DOI |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85147047066&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(18bcdf2e-a918-4e32-b3f0-396e583076cd).html |
Abstract
Dynamically controlling the post-translational modification of the ε-amino groups of lysine residues is critical for regulating many cellular events. Increasing studies have revealed that many important diseases, including cancer and neurological disorders, are associated with the malfunction of lysine deacylases and demethylases. Developing fluorescent probes that are capable of detecting lysine deacylase and demethylase activity is highly useful for interrogating their roles in epigenetic regulation and diseases. Due to the distinct substrate recognition of these epigenetic eraser enzymes, designing a universal strategy for detecting their activity poses substantial difficulty. Moreover, designing activity-based probes for differentiating their demethylation states is even more challenging and still remains largely unexplored. Herein, we report a universal strategy to construct probes that can detect the enzymatic activity of epigenetic “erasers” through NBD-based long-distance intramolecular reactions. The probes can be easily prepared by installing the O-NBD group at the C-terminal residue of specific peptide substrates by click chemistry. Based on this strategy, detecting the activity of lysine deacetylase, desuccinylase, or demethylase with superior sensitivity and selectivity has been successfully achieved through single-step probe development. Furthermore, the demethylase probe based on this strategy is capable of distinguishing different demethylation states by both absorption and fluorescence lifetime readout. We envision that these newly developed probes will provide powerful tools to facilitate drug discovery in epigenetics in the future. © 2023 American Chemical Society
Research Area(s)
- fluorogenic probe, post-translational modification, deacylase, desuccinylase, demethylase
Citation Format(s)
Universal Strategy to Develop Fluorogenic Probes for Lysine Deacylase/Demethylase Activity and Application in Discriminating Demethylation States. / Wei, Wenyu; Zhang, Jie; Xu, Zhiqiang et al.
In: ACS Sensors, Vol. 8, No. 1, 27.01.2023, p. 28-39.
In: ACS Sensors, Vol. 8, No. 1, 27.01.2023, p. 28-39.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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