Discovery of a fragment hit compound targeting D-Ala

D-Ala ligase of bacterial peptidoglycan biosynthesis

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

Povzetek

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.

Ključne besede

fragment-based drug discovery;hit triage;inhibitors;antibacterial agents;

Podatki

Jezik:	Angleški jezik
Leto izida:	2023
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL FFA - Fakulteta za farmacijo
UDK:	615.4:54:615.015.8
COBISS:	132472579
ISSN:	1475-6374
Št. ogledov:	594
Št. prenosov:	115
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	zaviralci;antibakterijska sredstva;odkrivanje zdravil na osnovi fragmentov;triaža zadetkov;Bakterijska rezistenca;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 387-397
Letnik:	ǂVol. ǂ38
Zvezek:	ǂiss. ǂ1
Čas izdaje:	2023
DOI:	10.1080/14756366.2022.2149745
ID:	17332123