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Environment-sensitive turn-on fluorescent probes for p53-MDM2 protein-protein interaction.

ABSTRACT: 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 in vitro and in cellulo. In particular probe 10, which had a K_i value of 0.03 ?M, displayed much better binding affinity compared to the positive control Nutlin-3, which had a K_i value of 0.23 ?M. 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.

SUBMITTER: Liu T

PROVIDER: S-EPMC6072338 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Environment-sensitive turn-on fluorescent probes for p53-MDM2 protein-protein interaction.

Liu Tingting T Jiang Yan Y Liu Zhenzhen Z Li Jin J Fang Kun K Zhuang Chunlin C Du Lupei L Fang Hao H Sheng Chunquan C Li Minyong M

MedChemComm 20170703 8

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 in vitro and in cellulo. In particular probe 10, which had a Ki value of 0.03 μM, displayed much better binding affinity compared to the positive control Nutlin-3, which had a Ki value of 0.23 μM. These no-wash environment-sensitive ...[more]

PMID: 30108877

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