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A proximity-induced covalent fluorescent probe for selective detection of bromodomain 4

Feng, Ling, Chhabra, Mohit, So, Wing Ho, Zhu, Qing, Xia, Jiang and Sun, Hongyan 2018. A proximity-induced covalent fluorescent probe for selective detection of bromodomain 4. Chinese Chemical Letters 29 (7) , pp. 1147-1150. 10.1016/j.cclet.2018.05.031

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Abstract

Lysine acetylation is one of the most prevalent and important posttranslational modifications (PTMs) in proteins. The process can be recognized by bromodomains (BRDs), which are a class of protein-interaction modules involved in chromatin remodeling and transcriptional activation. The development of BRD fluorescent probes will be useful for monitoring the activity of BRDs in living cells as well as aiding inhibitor development. Herein we designed a peptide-based probe based on the proximity-induced protein conjugation reaction. The peptide-based probe is capable of covalently and selectively reacting with the unique cysteine residue in the bromodomain through proximity effect. Our experimental data showed that the probe displayed noticeable fluorescence response upon addition of BRD4(1). In-gel fluorescence scanning demonstrated that BRD4(1) can be covalently labelled by the probe. Moreover, the probe was shown to selectively detect BRD4(1) over other proteins. We envision that the probe developed in this study will provide a useful tool to further investigate the biological roles of BRDs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: Elsevier
ISSN: 1001-8417
Date of Acceptance: 14 May 2018
Last Modified: 25 May 2021 16:00
URI: http://orca.cardiff.ac.uk/id/eprint/141497

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