論文 - 詳細
| RRC ID | 75218 |
|---|---|
| 著者 | Kudo Y, Konoki K, Yotsu-Yamashita M. |
| タイトル | Mass spectrometry-guided discovery of new analogs of bicyclic phosphotriester salinipostin and evaluation of their monoacylglycerol lipase inhibitory activity. |
| ジャーナル | Biosci Biotechnol Biochem |
| Abstract |
Natural products containing the highly unusual phosphotriester ring are known to be potent serine hydrolase inhibitors. The long-chain bicyclic enol-phosphotriester salinipostins (SPTs) from the marine actinomycete Salinispora have been identified as selective antimalarial agents. A potential regulatory function has been suggested for phosphotriesters based on their structural relationship with actinomycete signaling molecules and the prevalence of spt-like biosynthetic gene clusters across actinomycetes. In this study, we established a mass spectrometry-guided screening method for phosphotriesters focusing on their characteristic fragment ions. Applying this screening method to the SPT producer Salinispora tropica CNB-440, new SPT analogs (4-6) were discovered and their structures were elucidated by spectroscopic analyses. Previously known and herein-identified SPT analogs inhibited the activity of human monoacylglycerol lipase (MAGL), a key serine hydrolase in the endocannabinoid system, in the nanomolar range. Our method could be applied to the screening of phosphotriesters, potential serine hydrolase inhibitors and signaling molecules. |
| 巻・号 | 86(10) |
| ページ | 1333-1342 |
| 公開日 | 2022-9-23 |
| DOI | 10.1093/bbb/zbac131 |
| PII | 6653519 |
| PMID | 35918181 |
| MeSH | Actinobacteria* Antimalarials* Biological Products* Endocannabinoids Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology Humans Mass Spectrometry Monoacylglycerol Lipases / chemistry Monoacylglycerol Lipases / genetics Serine |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 一般微生物 | JCM 13857 |