DNA-encoded library screening on two validated enzymes of the peptidoglycan biosynthetic pathway

Proj, Matic (avtor), Bozovičar, Krištof (avtor), Hrast, Martina (avtor), Frlan, Rok (avtor), Gobec, Stanislav (avtor)

Screening 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.

• Jezik: Angleški jezik
• Ključne besede: antibacterial agents, DNA-encoded library, screening, inhibitors
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 4 str.
• Številčenje: Vol. 73, art. 128915
• PID: 20.500.12556/RUL-138728
• UDK: 615.4.54
• ISSN pri članku: 0960-894X
• DOI: 10.1016/j.bmcl.2022.128915
• COBISS.SI-ID: 117813507
• Datum objave v RUL: 11.08.2022

Gradivo je del revije

• Naslov: Bioorganic & medicinal chemistry letters
• Skrajšan naslov: Bioorg. med. chem. lett.
• Založnik: Elsevier
• ISSN: 0960-894X
• COBISS.SI-ID: 34486272

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: antibakterijska sredstva, DNA-kodirana knjižnica, inhibitorji