title: Kribellosides, novel RNA 5'-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6.
abstract: 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-1against S. cerevisiae.
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sawa
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Hayashi
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Umekita
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hatano
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Biochemistry, School of Pharmacy, Kitasato University, Tokyo, Japan.
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Mizumoto
authors.affiliation: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nomoto
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000037:antagonists & inhibitors*; D039903:Actinobacteria / Q000378:metabolism*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D017766:Acid Anhydride Hydrolases; C023090:RNA triphosphatase