Specific Turn-On Fluorescent Probe with Aggregation-Induced Emission Characteristics for SIRT1 Modulator Screening and Living-Cell Imaging.

SIRT1 is an important protein that catalyzes the nicotinamide adenine dinucleotide (NAD)(+)-dependent deacetylation reaction, which is regarded as a novel target to treat metabolic disorders and aging-related diseases. However, there is lack of appropriate approach for SIRT1 modulator screening and bioimaging of SIRT1 in living cells. We designed and synthesized a "turn-on" fluorescent probe by connecting a specifically recognized peptide to tetraphenylethene core. It exhibits excellent selectivity and sensitivity in homogeneous measurement of SIRT1 activity for screening both SIRT1 inhibitors and activators. 20(S)-ginsenoside Rg3 and ophiopogonin D' were found to activate SIRT1. It was also successfully applied to monitor SIRT1 modulation in the cardiomyocytes as well as in the wild-type and SIRT1(-/-) mesenchymal stem cells.