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

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

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.

• Language: English
• Keywords: antibacterial agents, DNA-encoded library, screening, inhibitors
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 4 str.
• Numbering: Vol. 73, art. 128915
• PID: 20.500.12556/RUL-138728
• UDC: 615.4.54
• ISSN on article: 0960-894X
• DOI: 10.1016/j.bmcl.2022.128915
• COBISS.SI-ID: 117813507
• Publication date in RUL: 11.08.2022

Record is a part of a journal

• Title: Bioorganic & medicinal chemistry letters
• Shortened title: Bioorg. med. chem. lett.
• Publisher: Elsevier
• ISSN: 0960-894X
• COBISS.SI-ID: 34486272

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: antibakterijska sredstva, DNA-kodirana knjižnica, inhibitorji