Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6
doi: 10.1038/ja.2016.161
pmid: 28074052
Kribellosides, novel RNA 5′-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6
Yeast capping enzymes differ greatly from those of mammalian, both structurally and mechanistically. Yeast-type capping enzyme repressors are therefore candidate antifungal drugs. The 5'-guanine-N7 cap structure of mRNAs are an essential feature of all eukaryotic organisms examined to date and is the first co-transcriptional modification of cellular pre-messenger RNA. Inhibitors of the RNA 5'-triphosphatase in yeast are likely to show fungicidal effects against pathogenic yeast such as Candida. We discovered a new RNA 5'-triphosphatase inhibitor, designated as the kribellosides, by screening metabolites from actinomycetes. Kribellosides belong to the alkyl glyceryl ethers. These novel compounds inhibit the activity of Cet1p (RNA 5'-triphosphatase) from Saccharomyces cerevisiae in vitro with IC50s of 5-8 μM and show antifungal activity with MICs ranging from 3.12 to 100 μg ml-1 against S. cerevisiae.
- Kitasato University Japan
Actinobacteria, Inhibitory Concentration 50, Antifungal Agents, Microbial Sensitivity Tests, Saccharomyces cerevisiae, Enzyme Inhibitors, Acid Anhydride Hydrolases
Actinobacteria, Inhibitory Concentration 50, Antifungal Agents, Microbial Sensitivity Tests, Saccharomyces cerevisiae, Enzyme Inhibitors, Acid Anhydride Hydrolases
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