| Autor: |
Fumihiro Ishikawa, Sho Konno, Hideaki Kakeya, Genzoh Tanabe |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Beilstein Journal of Organic Chemistry, Vol 20, Iss 1, Pp 445-451 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1860-5397 |
| DOI: |
10.3762/bjoc.20.39 |
| Popis: |
The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A-domains could attenuate the virulence of pathogens. 5’-O-N-(Aminoacyl or arylacyl)sulfamoyladenosine (AA-AMS) is a bisubstrate small-molecule inhibitor of the A-domains of NRPSs. However, the bacterial cell permeability of AA-AMS is typically a problem owing to its high hydrophilicity. In this study, we investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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