{Reference Type}: Journal Article
{Title}: Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics.
{Author}: Koppermann S;Cui Z;Fischer PD;Wang X;Ludwig J;Thorson JS;Van Lanen SG;Ducho C;
{Journal}: ChemMedChem
{Volume}: 13
{Issue}: 8
{Year}: 04 2018 23
{Factor}: 3.54
{DOI}: 10.1002/cmdc.201700793
{Abstract}: 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.