Discovery of Potential Antituberculosis Agents Targeted Methionine Aminopeptidase 1 of <i>Mycobacterium tuberculosis</i> by the Developed Fluorescent Probe

Tuberculosis (TB) is a chronic systemic infectious disease caused by Mycobacterium tuberculosis ( M. tuberculosis ). Methionine aminopeptidase 1 (MtMET-AP1) is a hydrolase that mediates the necessary post-translational N -terminal methionine excision (NME) of peptides during protein synthesis, which is necessary for bacterial proliferation and is a potential target for the treatment of tuberculosis. Based on the functional characteristics of MtMET-AP1, we developed an enzymatic activated near-infrared fluorescent probe DDAN-MT for rapid, highly selective, and real-time monitoring of endogenous MtMET-AP1 activity in M. tuberculosis . Using the probe DDAN-MT , a visually high-throughput screening technique was established, which obtained three potential inhibitors (GSK-J4 hydrochchloride, JX06, and lavendustin C) against MtMET-AP1 from a 2560 compounds library. More importantly, these inhibitors could inhibit the growth of M. tuberculosis H37Ra especially (MICs DDAN-MT , and MtMET-AP1 inhibitors were discovered as potential antituberculosis agents.