Arylazopyrazole-Based Photoswitchable Inhibitors Selective for Escherichia coli Dihydrofolate Reductase.
ACS Chem Biol
; 18(2): 340-346, 2023 02 17.
Article
em En
| MEDLINE
| ID: mdl-36662098
ABSTRACT
Selective inhibitors of Escherichia coli dihydrofolate reductase (eDHFR) are crucial chemical biology tools that have widespread clinical applications. We developed a set of eDHFR-selective photoswitchable inhibitors by derivatizing the structure of our previously reported methotrexate (MTX) azolog, azoMTX. Substitution of the skeletal p-phenylene group of azoMTX with bulky bis-alkylated arylazopyrazole moieties significantly increased its selectivity toward eDHFR over human DHFR. Owing to the physical properties of arylazopyrazoles, the new ligands exhibited nearly complete Z-to-E photoconversion and high thermostability of Z-isomers. In addition, real-time photoreversible control of eDHFR activity was achieved by alternatively switching the illumination light wavelengths.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidrofolato Desidrogenase
/
Escherichia coli
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article