Oral Disinfectants Inhibit Protein–Protein Interactions Mediated by the Anti-Apoptotic Protein Bcl-xL and Induce Apoptosis in Human Oral Tumor Cells

Authors

  • Dr. Martin Gräber,

    1. Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg
    2. Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dipl.-Chem. Michael Hell,

    1. Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany)
    2. Institute of Molecular Health Sciences, ETH Zurich, Schafmattstrasse 18, 8093 Zurich (Switzerland)
    Search for more papers by this author
    • These authors contributed equally to this work.

  • M. Sc. Corinna Gröst,

    1. Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Dr. Anders Friberg,

    1. Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg (Germany)
    2. Munich Center for Integrated Protein Science, Chair of Biomolecular NMR Spectroscopy, Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    3. Current address: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146 (USA)
    Search for more papers by this author
  • Bianca Sperl,

    1. Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany)
    Search for more papers by this author
  • Prof. Dr. Michael Sattler,

    1. Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg (Germany)
    2. Munich Center for Integrated Protein Science, Chair of Biomolecular NMR Spectroscopy, Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany)
    Search for more papers by this author
  • Prof. Dr. Thorsten Berg

    Corresponding author
    1. Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg
    2. Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany)
    • Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg===

    Search for more papers by this author

  • This work was generously supported by the Department of Molecular Biology (Director: Prof. Dr. Axel Ullrich) at the Max Planck Institute of Biochemistry (MPIB), the Center for Integrated Protein Science Munich (CIPSM), the BMBF (NGFN-2, grant 01GS0451 to T.B.), the Deutsche Krebshilfe (grant 108614 to T.B.), and the Deutsche Forschungsgemeinschaft (grant BE 4572/1-1 to T.B.). We thank Prof. Ho Sup Yoon (Nanyang Technological University, Singapore) for the Bcl-xL plasmid and protein backbone assignments. We extend our thanks to Judith Müller (MPIB) and the core facility of the MPIB for experimental support, and to Angela Hollis for critical reading of the manuscript. We are grateful to Prof. Dr. Wilhelm Krek (ETH Zurich) for supporting the work of M.H.

Abstract

original image

Chlorhexidine and alexidine have long been used as oral disinfectants by humans. Both compounds inhibit protein–protein interactions mediated by the anti-apoptotic protein Bcl-xL at physiologically relevant concentrations and induce apoptosis in a series of tumor cell lines derived from the tongue and pharynx (see picture). Inhibition of protein–protein interactions is a potential mode of action of drugs in current human use.

Ancillary