Duocarmycin Analogues Target Aldehyde Dehydrogenase 1 in Lung Cancer Cells

Authors

  • M. Sc. Tanja Wirth,

    1. Department Chemie, Center for Integrated Protein Science CIPSM, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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  • Dr. Kianga Schmuck,

    1. Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, 37033 Göttingen (Germany)
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  • Prof. Dr. Lutz F. Tietze,

    Corresponding author
    1. Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, 37033 Göttingen (Germany)
    • Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstr. 2, 37033 Göttingen (Germany)
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  • Prof. Dr. Stephan A. Sieber

    Corresponding author
    1. Department Chemie, Center for Integrated Protein Science CIPSM, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    • Department Chemie, Center for Integrated Protein Science CIPSM, Institute of Advanced Studies IAS, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
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  • We thank Mona Wolff and Burghard Cordes for excellent scientific support and Matthew Nodwell and Nina Mäusbacher for scientific discussions. S.S. was supported by the Deutsche Forschungsgemeinschaft (Emmy Noether), grant numbers SFB749 and FOR1406, an ERC starting grant, and the Center for Integrated Protein Science Munich CIPSM. T.W. thanks the TUM Graduate School for project funding. K.S. thanks the Fonds der Chemischen Industrie for a Ph.D. scholarship. L.F.T thanks the DFG and the Fonds der Chemischen Industrie for financial support.

Abstract

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Neue Ziele: Mithilfe von Proteomikstudien wurde nachgewiesen, dass Aldehyd-Dehydrogenase 1 eine zusätzliche oder alternative Zielverbindung von Duocarmycin sein könnte. Selektive Inhibierung dieses Enzyms in Lungenkrebszellen erklärt die Antitumoraktivität von Duocarmycinanaloga (siehe Schema).

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