2 research outputs found
Pintavedenoton suhteen kriittisimmät väyläosuudet liikenteen ja väylänpidon kannalta
<i>N</i>-Leucinyl benzenesulfonamides have been discovered
as a novel class of potent inhibitors of <i>E. coli</i> leucyl-tRNA
synthetase. The binding of inhibitors to the enzyme was measured by
using isothermal titration calorimetry. This provided information
on enthalpy and entropy contributions to binding, which, together
with docking studies, were used for structure–activity relationship
analysis. Enzymatic assays revealed that <i>N</i>-leucinyl
benzenesulfonamides display remarkable selectivity for <i>E.
coli</i> leucyl-tRNA synthetase compared to <i>S. aureus</i> and human orthologues. The simplest analogue of the series, <i>N</i>-leucinyl benzenesulfonamide (R = H), showed the highest
affinity against <i>E. coli</i> leucyl-tRNA synthetase and
also exhibited antibacterial activity against Gram-negative pathogens
(the best MIC = 8 μg/mL, <i>E. coli</i> ATCC 25922),
which renders it as a promising template for antibacterial drug discovery