Kribellosides, novel RNA 5'-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6
| Autor: | Masaki Hatano, Maya Umekita, Akio Nomoto, Kiyohisa Mizumoto, Manabu Yamasaki, Masayuki Igarashi, Ryuichi Sawa, Toshinobu Fujiwara, Chigusa Hayashi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Antifungal Agents Saccharomyces cerevisiae Repressor Microbial Sensitivity Tests Microbiology 03 medical and health sciences Inhibitory Concentration 50 Capping enzyme Drug Discovery Enzyme Inhibitors Pharmacology chemistry.chemical_classification biology RNA biology.organism_classification In vitro Yeast Acid Anhydride Hydrolases Actinobacteria 030104 developmental biology Enzyme chemistry Biochemistry Kribbella sp. MI481-42F6 |
| Zdroj: | The Journal of antibiotics. 70(5) |
| ISSN: | 1881-1469 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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