Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesis.
Fragment-based drug discovery
antibacterial agents
hit triage
inhibitors
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
entrez:
29
11
2022
pubmed:
30
11
2022
medline:
2
12
2022
Statut:
ppublish
Résumé
Bacterial resistance is an increasing threat to healthcare systems, highlighting the need for discovering new antibacterial agents. An established technique, fragment-based drug discovery, was used to target a bacterial enzyme Ddl involved in the biosynthesis of peptidoglycan. We assembled general and focused fragment libraries that were screened in a biochemical inhibition assay. Screening revealed a new fragment-hit inhibitor of DdlB with a Ki value of 20.7 ± 4.5 µM. Binding to the enzyme was confirmed by an orthogonal biophysical method, surface plasmon resonance, making the hit a promising starting point for fragment development.
Identifiants
pubmed: 36446617
doi: 10.1080/14756366.2022.2149745
pmc: PMC9718554
doi:
Substances chimiques
Peptidoglycan
0
Anti-Bacterial Agents
0
Ligases
EC 6.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
387-397Références
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