ACS Medicinal Chemistry Letters
Letter
Lung Association (2018-02). We acknowledge partial financial
support by the DFG (GRK 2158, P4 for H.G.). We gratefully
acknowledge the NMR and MS services of the University of
Zurich and F. Fazzi and G. Uzunidis for skillful laboratory
assistance. We further thank A. Siegle and O. Trapp (LMU
̈
Munchen) for using the HPLC in their research groups and R.
Wehlauch and J. Michel for proofreading the manuscript.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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sı
Supplementary Figures S1 and S2, experimental proce-
dures and methods, characterization data, H and 13C
1
NMR spectra, supplementary MIC tables, and computa-
ABBREVIATIONS
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AUTHOR INFORMATION
Corresponding Author
CDI C. difficile infection; MIC minimum inhibitory concen-
tration; RNAP RNA polymerase; cryo-EM cryo-electron
microscopy; HPLC high performance liquid chromatography;
PEG polyethylene glycol.
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Karl Gademann − Department of Chemistry, University of Zurich,
̈
REFERENCES
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Authors
Andrea Dorst − Department of Chemistry, University of Zurich,
8057 Zurich, Switzerland
Regina Berg − Department of Chemistry, University of Zurich,
8057 Zurich, Switzerland
Christoph G. W. Gertzen − Institute for Pharmaceutical and
Medicinal Chemistry, Heinrich Heine University Dusseldorf,
40225 Dusseldorf, Germany
Daniel Schafle − Institute of Medical Microbiology, University of
Zurich, 8006 Zurich, Switzerland
Katja Zerbe − Department of Chemistry, University of Zurich,
̈
8057 Zurich, Switzerland
Myriam Gwerder − Department of Chemistry, University of
Zurich, 8057 Zurich, Switzerland
Simon D. Schnell − Department of Chemistry, University of
Zurich, 8057 Zurich, Switzerland
Peter Sander − Institute of Medical Microbiology and National
Center for Mycobacteria, University of Zurich, 8006 Zurich,
Switzerland
̈
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̈
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Holger Gohlke − Institute for Pharmaceutical and Medicinal
Chemistry, Heinrich Heine University Dusseldorf, 40225
̈
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Complete contact information is available at:
Author Contributions
⊥A.D. and R.B. contributed equally. The manuscript was written
through contributions of all authors. A.D., R.B., and K.G.
designed the study. A.D., R.B., and S.D.S. carried out the
synthesis and characterization of the derivatives. C.G.W.G., and
H.G. performed the homology modeling and computational
studies. D.S. and P.S. developed the MIC tests for M. tuberculosis
and performed the biological evaluation of the derivatives. K.Z.
and M.G. performed the MIC tests against S. aureus and B.
subtilis. A.D., R.B., and K.G. analyzed and discussed the results.
A.D.,R.B., and K.G. wrote the manuscript. All authors have given
approval to the final version of the manuscript.
Notes
The authors declare the following competing financial
interest(s): A patent application (WO2019135010A1,
EP18150671.8A) was filed Jan 8th, 2018 that includes
antibiotics presented in this work.
ACKNOWLEDGMENTS
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We thank the Swiss National Science Foundation for financial
support (200021_182043 (K.G.) and 31003A_153349/1
(P.S.)). Work in the laboratory of P.S. is supported by Swiss
F
ACS Med. Chem. Lett. XXXX, XXX, XXX−XXX