DNA-encoded library screening on two validated enzymes of the peptidoglycan biosynthetic pathwayProj, Matic (Avtor) Bozovičar, Krištof (Avtor) Hrast Rambaher, Martina (Avtor) Frlan, Rok (Avtor) Gobec, Stanislav (Avtor) antibacterial agentsDNA-encoded libraryscreeninginhibitorsScreening of DNA-encoded libraries is an emerging technology for discovering hits against protein targets. With the recent launch of the DELopen platform, a facile screening of 4.4 billion compounds is available to accelerate the drug discovery process. Here we report an affinity-based screening of the DELopen library for the first time. The screening was performed against two bacterial enzymes of the peptidoglycan biosynthetic pathway, N-acetylglucosamine-enolpyruvyl transferase (MurA) and D-alanine:D-alanine ligase (DdlB). Several binders were obtained and selected for off-DNA synthesis. Hits with confirmed inhibitory potency were deconstructed into smaller fragments. In this way, two new MurA inhibitors with antibacterial activity were obtained and are available for further optimization.20222022-08-11 07:11:34Članek v reviji138728sl