%0 Journal Article
%T Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics.
%A Koppermann S
%A Cui Z
%A Fischer PD
%A Wang X
%A Ludwig J
%A Thorson JS
%A Van Lanen SG
%A Ducho C
%J ChemMedChem
%V 13
%N 8
%D 04 2018 23
%M 29438582
%F 3.54
%R 10.1002/cmdc.201700793
%X Muraymycins are a subclass of antimicrobially active uridine-derived natural products. Biological data on several muraymycin analogues have been reported, including some inhibitory in vitro activities toward their target protein, the bacterial membrane enzyme MraY. However, a structure-activity relationship (SAR) study on naturally occurring muraymycins based on such in vitro data has been missing so far. In this work, we report a detailed SAR investigation on representatives of the four muraymycin subgroups A-D using a fluorescence-based in vitro MraY assay. For some muraymycins, inhibition of MraY with IC50 values in the low-picomolar range was observed. These inhibitory potencies were compared with antibacterial activities and were correlated to modelling data derived from a previously reported X-ray crystal structure of MraY in complex with a muraymycin inhibitor. Overall, these results will pave the way for the development of muraymycin analogues with optimized properties as antibacterial drug candidates.