Beilstein J. Org. Chem.2024,20, 721–733, doi:10.3762/bjoc.20.66
gramicidinSsynthetase GrsB [44]. Combined with the peptidyl carrier protein, GrsB PCP-TE was tested by using corresponding pentapeptides NAC thioester and thiophenol thioester, which led to the formation of the desired cyclic decapeptide lactam gramicidin S (9) through a sequential dimerization and
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Graphical Abstract
Scheme 1:
Brief introduction of thioesterase (TE) domain. (a) NRPS and PKS assembly lines. (b) Mechanism of T...
Beilstein J. Org. Chem.2024,20, 445–451, doi:10.3762/bjoc.20.39
synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors.
Keywords: adenylation domain inhibitor; gramicidinSsynthetase; natural product; nonribosomal peptide; nonribosomal peptide synthetase
introduced a pegylated biotin linker at the 2′-OH group of ʟ-Phe-AMS and confirmed that the probe retains the binding activities toward the A-domain of GrsA, a gramicidinSsynthetase. Aldrich et al. developed a Sal-AMS-based activity-based probe (ABP) to profile MbtA in M. tuberculosis [12]. In contrast, we
present study, we investigated the influence of the introduction of several functional groups at the 2′-OH group of the AMS scaffold on both the binding affinities for A-domains and cell permeability (Figure 2c and Figure 3). We selected the ʟ-Phe-selective A-domain of the gramicidinSsynthetase GrsA
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Graphical Abstract
Figure 1:
Biosynthesis of gramicidin S. Modules comprise the PCP, A, E, C, and TE domains. PCP, peptidyl carr...