D-Ala ligase of bacterial peptidoglycan biosynthesis
Matic Proj (Author), Martina Hrast (Author), Gregor Bajc (Author), Rok Frlan (Author), Anže Meden (Author), Matej Butala (Author), Stanislav Gobec (Author)

Abstract

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.

Keywords

fragment-based drug discovery;hit triage;inhibitors;antibacterial agents;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 615.4:54:615.015.8
COBISS: 132472579 Link will open in a new window
ISSN: 1475-6374
Views: 594
Downloads: 115
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: zaviralci;antibakterijska sredstva;odkrivanje zdravil na osnovi fragmentov;triaža zadetkov;Bakterijska rezistenca;
Type (COBISS): Article
Pages: str. 387-397
Volume: ǂVol. ǂ38
Issue: ǂiss. ǂ1
Chronology: 2023
DOI: 10.1080/14756366.2022.2149745
ID: 17332123