Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesis

Proj, Matic (avtor), Hrast, Martina (avtor), Bajc, Gregor (avtor), Frlan, Rok (avtor), Meden, Anže (avtor), Butala, Matej (avtor), Gobec, Stanislav (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: fragment-based drug discovery, hit triage, inhibitors, antibacterial agents
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: Str. 387-397
• Številčenje: Vol. 38, no. 11
• PID: 20.500.12556/RUL-142961
• UDK: 615.4:54:615.015.8
• ISSN pri članku: 1475-6374
• DOI: 10.1080/14756366.2022.2149745
• COBISS.SI-ID: 132472579
• Datum objave v RUL: 06.12.2022

PROJ, Matic, HRAST, Martina, BAJC, Gregor, FRLAN, Rok, MEDEN, Anže, BUTALA, Matej in GOBEC, Stanislav, 2023, Discovery of a fragment hit compound targeting D-Ala:D-Ala ligase of bacterial peptidoglycan biosynthesis. Journal of enzyme inhibition and medicinal chemistry [na spletu]. 2023. Vol. 38, no. 11, p. 387–397. [Dostopano 5 maj 2025]. DOI 10.1080/14756366.2022.2149745. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=142961

Gradivo je del revije

• Naslov: Journal of enzyme inhibition and medicinal chemistry
• Skrajšan naslov: J. enzyme inhib. med. chem.
• Založnik: Taylor & Francis
• ISSN: 1475-6374
• COBISS.SI-ID: 22763225

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: zaviralci, antibakterijska sredstva, odkrivanje zdravil na osnovi fragmentov, triaža zadetkov, bakterijska rezistenca