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Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family
Author(s) -
Krahn Daniel,
Heilmann Geronimo,
Vogel Felix C. E.,
Papadopoulos Chrisovalantis,
Zweerink Susanne,
Kaschani Farnusch,
Meyer Hemmo,
Roesch Alexander,
Kaiser Markus
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001577
Subject(s) - natural product , computational biology , family member , chemistry , mode of action , oxidative phosphorylation , stereochemistry , combinatorial chemistry , inhibitory postsynaptic potential , biochemistry , structure–activity relationship , chemical structure , biology , in vitro , medicine , organic chemistry , neuroscience , family medicine
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Ōmura 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.