Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesisProj, Matic (Avtor) Hrast Rambaher, Martina (Avtor) Bajc, Gregor (Avtor) Frlan, Rok (Avtor) Meden, Anže (Avtor) Butala, Matej (Avtor) Gobec, Stanislav (Avtor) fragment-based drug discoveryhit triageinhibitorsantibacterial agentsBacterial 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.20232022-12-06 10:53:47Članek v reviji142961sl