Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family

Overview

Journal Chemistry

Specialty Chemistry

Date 2020 Apr 7

PMID 32250484

Citations 3

Authors

Daniel Krahn

Geronimo Heilmann

Felix C E Vogel

Chrisovalantis Papadopoulos

Susanne Zweerink

Farnusch Kaschani

Hemmo Meyer

Alexander Roesch

Markus Kaiser

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Synthesis and Anticancer Activity Assessment of Zelkovamycin Analogues.

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Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin.

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PMID: 34847153 PMC: 8631618. DOI: 10.1371/journal.pone.0260413.

Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family.

Krahn D, Heilmann G, Vogel F, Papadopoulos C, Zweerink S, Kaschani F Chemistry. 2020; 26(39):8524-8531.

PMID: 32250484 PMC: 7383741. DOI: 10.1002/chem.202001577.

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