期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 26, 期 39, 页码 8524-8531出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202001577
关键词
argyrin; bioactivity; cyclopeptides; natural products; zelkovamycin
资金
- DFG-funded [CRC1093]
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Omura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displays structural similarities as well as differences to the argyrin NP family, a class of peptidic NPs with promising anticancer activities and diverse mode-of-action at the molecular level. By a combination of structure elucidation experiments, the first total synthesis of zelkovamycin and bioassays, the zelkovamycin configuration was determined and its previously proposed molecular structure was revised. The full structure assignment proves zelkovamycin as an additional member of the argyrins with however unique OXPHOS inhibitory properties. Zelkovamycin may therefore not only serve as a new starting point for chemical inhibitors of the OXPHOS system, but also guide customized argyrin NP isolation and biosynthesis studies.
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