Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

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.

Beilstein J. Org. Chem. 2024, 20, 445–451. doi:10.3762/bjoc.20.39

Source: Beilstein Journal of Organic Chemistry - February 26, 2024 Category: Chemistry Authors: Beilstein Journal of Organic Chemistry - Syndicated Feeds Tags: adenylation domain inhibitor gramicidin S synthetase natural product nonribosomal peptide nonribosomal peptide synthetase Full Research Paper Source Type: research