Methionine aminopeptidase 2 (MetAP-2) catalyzes the removal of methionine from the amino-terminus of proteins or peptides and is a known target for anti-tumor therapy. In this study, we developed an enzyme-activated fluorescent probe, DDAO-BMT, specifically for the real-time detection of endogenous MetAP-2. This probe enables the determination of extracellular MetAP-2 activity and visual monitoring of intracellular MetAP-2. Additionally, Sappan Lignum was identified as an active herbal medicine against MetAP-2, with brazilin identified as its key active constituent. Brazilin also exhibited a significant anti-tumor effect, including the inhibition on proliferation, migration, and invasion of tumor cells, and the preliminary mechanism of its activity against cancer has been elucidated. The use of this probe facilitates the monitoring of endogenous MetAP-2 in complex biological system, aiding in the discovery of novel active compounds for cancer treatment.
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