| 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
|
| リソース情報 |
| 一般微生物 |
JCM 13857 |
