Artigo Acesso aberto Revisado por pares

Oral Disinfectants Inhibit Protein–Protein Interactions Mediated by the Anti‐Apoptotic Protein Bcl‐x L and Induce Apoptosis in Human Oral Tumor Cells

2013; Wiley; Volume: 52; Issue: 16 Linguagem: Inglês

10.1002/anie.201208889

ISSN

1521-3773

Autores

Martin Gräber, Michael P. Hell, Corinna Gröst, Anders Friberg, Bianca Sperl, Michael Sattler, Thorsten Berg,

Tópico(s)

Synthesis of Tetrazole Derivatives

Resumo

Angewandte Chemie International EditionVolume 52, Issue 16 p. 4487-4491 Communication Oral Disinfectants Inhibit Protein–Protein Interactions Mediated by the Anti-Apoptotic Protein Bcl-xL and Induce Apoptosis in Human Oral Tumor Cells† Dr. Martin Gräber, Dr. Martin Gräber Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany) These authors contributed equally to this work.Search for more papers by this authorDipl.-Chem. Michael Hell, Dipl.-Chem. Michael Hell 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 Molecular Health Sciences, ETH Zurich, Schafmattstrasse 18, 8093 Zurich (Switzerland) These authors contributed equally to this work.Search for more papers by this authorM. Sc. Corinna Gröst, M. Sc. Corinna Gröst Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg These authors contributed equally to this work.Search for more papers by this authorDr. Anders Friberg, Dr. Anders Friberg Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg (Germany) Munich Center for Integrated Protein Science, Chair of Biomolecular NMR Spectroscopy, Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany) Current address: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146 (USA)Search for more papers by this authorBianca Sperl, Bianca Sperl 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 authorProf. Dr. Michael Sattler, Prof. Dr. Michael Sattler Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg (Germany) 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 authorProf. Dr. Thorsten Berg, Corresponding Author Prof. Dr. Thorsten Berg [email protected] Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg 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 Dr. Martin Gräber, Dr. Martin Gräber Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg Department of Molecular Biology, Max Planck Institute of Biochemistry, and Center for Integrated Protein Science Munich (CIPSM), Am Klopferspitz 18, 82152 Martinsried (Germany) These authors contributed equally to this work.Search for more papers by this authorDipl.-Chem. Michael Hell, Dipl.-Chem. Michael Hell 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 Molecular Health Sciences, ETH Zurich, Schafmattstrasse 18, 8093 Zurich (Switzerland) These authors contributed equally to this work.Search for more papers by this authorM. Sc. Corinna Gröst, M. Sc. Corinna Gröst Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg These authors contributed equally to this work.Search for more papers by this authorDr. Anders Friberg, Dr. Anders Friberg Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg (Germany) Munich Center for Integrated Protein Science, Chair of Biomolecular NMR Spectroscopy, Department of Chemistry, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching (Germany) Current address: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146 (USA)Search for more papers by this authorBianca Sperl, Bianca Sperl 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 authorProf. Dr. Michael Sattler, Prof. Dr. Michael Sattler Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg (Germany) 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 authorProf. Dr. Thorsten Berg, Corresponding Author Prof. Dr. Thorsten Berg [email protected] Institute of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig (Germany) http://www.uni-leipzig.de/∼tberg 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 First published: 19 March 2013 https://doi.org/10.1002/anie.201208889Citations: 17 † 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. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract 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. Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Filename Description anie_201208889_sm_miscellaneous_information.pdf2.6 MB miscellaneous_information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1J. A. Wells, C. L. McClendon, Nature 2007, 450, 1001. 2C. Tse, A. R. Shoemaker, J. Adickes, M. G. Anderson, J. Chen, S. Jin, E. F. Johnson, K. C. Marsh, M. J. Mitten, P. Nimmer, L. Roberts, S. K. Tahir, Y. Xiao, X. Yang, H. Zhang, S. Fesik, S. H. Rosenberg, S. W. Elmore, Cancer Res. 2008, 68, 3421. 3M. A. Dechantsreiter, E. Planker, B. Matha, E. Lohof, G. Holzemann, A. Jonczyk, S. L. Goodman, H. Kessler, J. Med. Chem. 1999, 42, 3033. 4C. Mas-Moruno, F. Rechenmacher, H. Kessler, Anti-Cancer Agents Med. Chem. 2010, 10, 753. 5H. Carol, C. P. Reynolds, M. H. Kang, S. T. Keir, J. M. Maris, R. Gorlick, E. A. Kolb, C. A. Billups, B. Geier, R. T. 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