Liu Tingting, Jiang Yan, Liu Zhenzhen, Li Jin, Fang Kun, Zhuang Chunlin, Du Lupei, Fang Hao, Sheng Chunquan, Li Minyong
Department of Medicinal Chemistry , Key Laboratory of Chemical Biology (MOE) , School of Pharmacy , Shandong University , Jinan , Shandong 250012 , China . Email:
Department of Medicinal Chemistry , School of Pharmacy , Second Military Medical University , 325 Guohe Road , Shanghai 200433 , China . Email:
Medchemcomm. 2017 Jul 3;8(8):1668-1672. doi: 10.1039/c7md00287d. eCollection 2017 Aug 1.
A series of probes with a turn-on switch for the p53-MDM2 protein-protein interaction were developed. After careful evaluation, these small molecule fluorescent probes exhibited high practical activity and selectivity and . In particular probe 10, which had a value of 0.03 μM, displayed much better binding affinity compared to the positive control Nutlin-3, which had a value of 0.23 μM. These no-wash environment-sensitive turn-on fluorescent probes have been successfully applied to imaging p53-MDM2 interaction in the human lung cancer cell line A549 (wild-type p53) at the micromolar level. Therefore, these fluorescent probes are expected to be used in drug screening and cell staining in p53-MDM2 fields, as well as in pathological and physiological studies of the p53-MDM2 interaction.
开发了一系列用于p53-MDM2蛋白质-蛋白质相互作用的具有开启开关的探针。经过仔细评估，这些小分子荧光探针表现出高实际活性和选择性。特别是探针10，其解离常数为0.03 μM，与阳性对照Nutlin-3（解离常数为0.23 μM）相比，显示出更好的结合亲和力。这些无需洗涤的环境敏感型开启荧光探针已成功应用于在微摩尔水平成像人肺癌细胞系A549（野生型p53）中的p53-MDM2相互作用。因此，这些荧光探针有望用于p53-MDM2领域的药物筛选和细胞染色，以及p53-MDM2相互作用的病理和生理研究。
