Résumé
Anin situscreening assay for UDP-galactopyranose mutase (UGM, an essential enzyme ofM. tuberculosiscell wall biosynthesis) has been developed to discover novel UGM inhibitors. The approach is based on the amide-forming reaction of an amino acid core with various cinnamic acids, followed by a direct fluorescence polarization assay to identify the best UGM binders without isolation and purification of the screened ligands. This assay allows us to perform one-pot high-throughput synthesis and screening of enzyme inhibitors in a 384-well plate format. UGM ligands were successfully identified by this technology and their inhibition levels were established from pure synthetic compoundsin vitroand in a whole cell antibacterial assay. This study provides a blueprint for designing enamide structures as new UGM inhibitors and anti-mycobacterial agents.
langue originale | Anglais |
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Pages (de - à) | 1818-1826 |
Nombre de pages | 9 |
journal | Organic and Biomolecular Chemistry |
Volume | 19 |
Numéro de publication | 8 |
Les DOIs | |
Etat de la publication | Publié - 28 févr. 2021 |