2. Academic Validation
  3. Towards selective peptide deformylase inhibitors: A mass spectrometry-based evaluation of in cellulo activity of actinonin and bromoindole derivatives

Towards selective peptide deformylase inhibitors: A mass spectrometry-based evaluation of in cellulo activity of actinonin and bromoindole derivatives

  • Eur J Med Chem. 2026 Apr 15:308:118678. doi: 10.1016/j.ejmech.2026.118678.
Nathalie Bachmann 1,  André Schultz 1,  Manuela Zouatom 2,  Tianyi Zhou 2,  Carsten Degenhart 3,  Uwe Koch 3,  Sina Schäkermann 1,  Julia Hüning 1,  Sascha Heinrich 1,  Michael Dal Molin 4,  Mia-Lisa Zischinsky 3,  Sylvain Tourel 3,  Anne-Kathrin Klebl 3,  Jan Rybniker 5,  Bert M Klebl 3,  Jürgen Scherkenbeck 2,  Julia E Bandow 6
Affiliations

Affiliations

  • 1 Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Universitätsstraße 150, Bochum, 44801, Germany.
  • 2 Organic Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, Wuppertal, 42119, Germany.
  • 3 Lead Discovery Center GmbH, Otto-Hahn-Strasse 15, Dortmund, 44227, Germany.
  • 4 Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, Kerpener Str. 62, Cologne, 50937, Germany; Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch Str. 21, Cologne, 50931, Germany.
  • 5 Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, Kerpener Str. 62, Cologne, 50937, Germany; Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch Str. 21, Cologne, 50931, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
  • 6 Applied Microbiology, Faculty of Biology and Biotechnology, Ruhr University Bochum, Universitätsstraße 150, Bochum, 44801, Germany. Electronic address: julia.bandow@rub.de.
PMID: 41719802 DOI: 10.1016/j.ejmech.2026.118678
Abstract

Peptide deformylase plays a crucial role in prokaryotic translation and constitutes an Antibiotic target previously addressed in clinical trials. In eukaryotes, mitochondrial translation also relies on peptide deformylase, necessitating Antibiotic development to aim for selective inhibition of the Bacterial enzymes. In the present study, we investigated two compound series: derivatives of actinonin and compounds containing a 5-bromoindole scaffold. Antibacterial activity was evaluated by microdilution-based minimal inhibitory concentration assay and selectivity investigated using human peripheral blood mononuclear cells. In vitro peptide deformylase inhibition was compared for the Escherichia coli and human enzyme. To validate peptide deformylase inhibition in the Bacterial cell, a mass spectrometric analysis directly coupled to the minimal inhibitory concentration assay was developed for the model organism Bacillus subtilis. Two compounds originating from this work (ZHO-119, ZHO-197) showed Antibacterial activity comparable to actinonin. They both were highly for the Bacterial enzyme selective in vitro and displayed no cytotoxicity. The mass spectrometry-based analysis indicates that in addition to peptide deformylase, ZHO-197 very effectively inhibits Bacterial methionine Aminopeptidase, the metallo-enzyme that removes the deformylated N-terminal methionine.

Keywords

5-Bromoindole; Actinonin; Mass spectrometry; Mode of action; Natural products; Peptide deformylase.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z