Identification of inhibitors of UDP-galactopyranose mutase via combinatorial in situ screening.
Org Biomol Chem
; 19(8): 1818-1826, 2021 03 04.
Article
em En
| MEDLINE
| ID: mdl-33565547
ABSTRACT
An in situ screening assay for UDP-galactopyranose mutase (UGM, an essential enzyme of M. tuberculosis cell 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 compounds in vitro and in a whole cell antibacterial assay. This study provides a blueprint for designing enamide structures as new UGM inhibitors and anti-mycobacterial agents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cinamatos
/
Transferases Intramoleculares
/
Inibidores Enzimáticos
/
Aminoácidos
/
Antituberculosos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Org Biomol Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article