A highly sensitive fluorescent light-up probe for real-time detection of the endogenous protein target and its antagonism in live cells

摘要: Real-time detection and monitoring of cancer-related biomolecular interactions in live cells are paramount importance for disease diagnostics drug screening. Herein, we developed a target-specific fluorescent light-up probe cellular Mdm2, the key negative regulator p53 tumour suppressor protein. Conjugation uniquely designed fluorogen (TPECM) with aggregation induced-emission properties, to specific p53-derived peptide (12.1Pep) targeting yielded cell-permeable (TPECM–12.1Pep) turn-on fluorescence properties real-time cell imaging Mdm2. This is almost non-fluorescent its isolated state but highly emissive upon binding enabling quantitative both Mdm2 antagonism. Using model compound (Nutlin-3a), demonstrate that as-developed probes can be used screen p53–Mdm2 inhibiting candidates, vitro cells. Furthermore, activity accurately monitored using fluorescently activated sorting machine. These features will expedite research areas discovery, clinical fundamental biology.