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Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase

Cell. 2017-06; 
Maffioli SI, Zhang Y, Degen D, Carzaniga T, Del Gatto G, Serina S, Monciardini P, Mazzetti C, Guglierame P, Candiani G, Chiriac AI, Facchetti G, Kaltofen P, Sahl HG, Dehò G, Donadio S, Ebright RH.
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PCR and Cloning 5-GCTCAAGAAACTCAAGAAGTTTCTGAAACAACTGAC-3 and 5-GTCAATGCTTTTTACTGCCAACAAACTCAGAC-3 for rpoC), 5 U Taq DNA polymerase (Genscript) Get A Quote

摘要

Drug-resistant bacterial pathogens pose an urgent public-health crisis. Here, we report the discovery, from microbial-extract screening, of a nucleoside-analog inhibitor that inhibits bacterial RNA polymerase (RNAP) and exhibits antibacterial activity against drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a natural product comprising a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6'-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, inhibits bacterial growth in culture, and clears infection in a mouse model of Streptococcus pyogenes peritonitis. PUM inhibits RNAP through a binding site on RNAP (the NTP addition site) and mechanism (competi... More

关键词

Pseudouridimycin (PUM); RNA polymerase; RNA polymerase inhibitor; antibacterial; antibiotic; antimicrobial resistance; microbial extract screening; nucleoside-analog inhibitor; transcription; transcription inhibitor