| Autor: |
Proj M; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Ljubljana, Ljubljana, Slovenia., Hrast M; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Ljubljana, Ljubljana, Slovenia., Bajc G; Biotechnical Faculty, Department of Biology, University of Ljubljana, Ljubljana, Slovenia., Frlan R; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Ljubljana, Ljubljana, Slovenia., Meden A; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Ljubljana, Ljubljana, Slovenia., Butala M; Biotechnical Faculty, Department of Biology, University of Ljubljana, Ljubljana, Slovenia., Gobec S; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Ljubljana, Ljubljana, Slovenia. |
| Abstrakt: |
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. |
