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Lookup NU author(s): Professor Yen Nee Tan
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Real-time detection and monitoring of cancer-related biomolecular interactions in live cells are of paramount importance for disease diagnostics and drug screening. Herein, we developed a target-specific fluorescent light-up probe for cellular detection of Mdm2, the key negative regulator of the p53 tumour suppressor protein. Conjugation of a uniquely designed fluorogen (TPECM) with aggregation induced-emission properties, to a specific p53-derived peptide (12.1Pep) targeting Mdm2, yielded a cell-permeable probe (TPECM–12.1Pep) with turn-on fluorescence properties for real-time live cell imaging of Mdm2. This specific light-up probe is almost non-fluorescent in its isolated state but is highly emissive upon binding to Mdm2, enabling quantitative detection of both Mdm2 and its antagonism. Using a model compound (Nutlin-3a), we demonstrate that the as-developed probes can be used to screen p53–Mdm2 inhibiting drug candidates, both in vitro and in cells. Furthermore, the probe activity can be accurately monitored in cells using a fluorescently activated cell sorting machine. These features will expedite research in the areas of drug discovery, clinical diagnostics and fundamental cell biology.
Author(s): Geng J, Goh WLP, Zhang C, Lane DP, Liu B, Ghadessy FJ, Tan YN
Publication type: Article
Publication status: Published
Journal: Journal of Materials Chemistry B
Year: 2015
Volume: 3
Issue: 29
Pages: 5933-5937
Print publication date: 07/08/2015
Online publication date: 19/06/2015
Acceptance date: 18/06/2015
Date deposited: 07/04/2020
ISSN (print): 2050-750X
ISSN (electronic): 2050-7518
Publisher: Royal Society of Chemistry
URL: https://doi.org/10.1039/c5tb00819k
DOI: 10.1039/c5tb00819k
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