Single-step fluorescent probes to detect decrotonylation activity of HDACs through intramolecular reactions
Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review
Author(s)
Related Research Unit(s)
Detail(s)
Original language | English |
---|---|
Article number | 113120 |
Journal / Publication | European Journal of Medicinal Chemistry |
Volume | 212 |
Online published | 30 Dec 2020 |
Publication status | Published - 15 Feb 2021 |
Link(s)
Abstract
Lysine crotonylation plays vital roles in gene transcription and cellular metabolism. Nevertheless, methods for dissecting the molecular mechanisms of decrotonyaltion remains limited. So far, there is no single-step fluorescent method developed for enzymatic decrotonylation activity detection. The major difficulty is that the aliphatic crotonylated lysine doesn't allow π-conjugation to a fluorophore and decrotonylation can not modulate the electronic state directly. Herein, we have designed and synthesized two activity-based single-step fluorogenic probes KTcr-I and KTcr-II for detecting enzymatic decrotonylation activity. These two probes can be recognized by histone deacetylases and undergo intramolecular nucleophilic exchange reaction to generate fluorescence signal. Notably, peptide sequence-dependent effect was observed. KTcr-I can be recognized by Sirt2 more effectively, while KTcr-II with LGKcr peptide sequence preferentially reacted with HDAC3. Compared to other methods of studying enzymatic decrotonylation activity, our single-step fluorescent method has a number of advantages, such as facileness, high sensitivity, cheap facility and little material consumed. We envision that the probes developed in this study will provide useful tools to screen inhibitors which suppress the decrotonylation activity of HDACs. Such probes will be useful for further delineating the roles of decrotonylation enzyme and aid in biomarker identification and drug discovery.
Research Area(s)
- Decrotonylation, Fluorescent probe, Histone deacetylases, Intramolecular reaction, Single-step, Sirtuin
Citation Format(s)
Single-step fluorescent probes to detect decrotonylation activity of HDACs through intramolecular reactions. / Xie, Yusheng; Yang, Liu; Chen, Qingxin; Zhang, Jie; Feng, Ling; Chen, Jian Lin; Hao, Quan; Zhang, Liang; Sun, Hongyan.
In: European Journal of Medicinal Chemistry, Vol. 212, 113120, 15.02.2021.Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review