Title: Discovery of Low‐Molecular‐Weight Ligands for the AF6 PDZ Domain
Abstract: Angewandte Chemie International EditionVolume 45, Issue 23 p. 3790-3795 Communication Discovery of Low-Molecular-Weight Ligands for the AF6 PDZ Domain† Mangesh Joshi, Mangesh Joshi Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorCarolyn Vargas, Carolyn Vargas Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorPrisca Boisguerin Dr., Prisca Boisguerin Dr. Institut für Medizinische Immunologie, Charité-Universitätsmedizin Berlin, Hessische Strasse 3–4, 10115 Berlin, GermanySearch for more papers by this authorAnnette Diehl Dr., Annette Diehl Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorGerd Krause Dr., Gerd Krause Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorPeter Schmieder Dr., Peter Schmieder Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorKarin Moelling Dr., Karin Moelling Dr. Institut für Medizinische Virologie, Universität Zürich, 8028 Zürich, SwitzerlandSearch for more papers by this authorVolker Hagen Dr., Volker Hagen Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorMarkus Schade Dr., Markus Schade Dr. [email protected] Combinature Biopharm AG, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94894-038Search for more papers by this authorHartmut Oschkinat Prof. Dr., Hartmut Oschkinat Prof. Dr. [email protected] Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this author Mangesh Joshi, Mangesh Joshi Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorCarolyn Vargas, Carolyn Vargas Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorPrisca Boisguerin Dr., Prisca Boisguerin Dr. Institut für Medizinische Immunologie, Charité-Universitätsmedizin Berlin, Hessische Strasse 3–4, 10115 Berlin, GermanySearch for more papers by this authorAnnette Diehl Dr., Annette Diehl Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorGerd Krause Dr., Gerd Krause Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorPeter Schmieder Dr., Peter Schmieder Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorKarin Moelling Dr., Karin Moelling Dr. Institut für Medizinische Virologie, Universität Zürich, 8028 Zürich, SwitzerlandSearch for more papers by this authorVolker Hagen Dr., Volker Hagen Dr. Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this authorMarkus Schade Dr., Markus Schade Dr. [email protected] Combinature Biopharm AG, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94894-038Search for more papers by this authorHartmut Oschkinat Prof. Dr., Hartmut Oschkinat Prof. Dr. [email protected] Leibniz-Institut für Molekulare Pharmakologie FMP, Robert-Roessle-Strasse 10, 13125 Berlin, Germany, Fax: (+49) 30-94793-169Search for more papers by this author First published: 24 May 2006 https://doi.org/10.1002/anie.200503965Citations: 34 † This work was supported by grants from the European Community (QLK3-2000-00924-SH2 Libraries) and the Deutsche Forschungsgemeinschaft (DFG) (OS 106/4-2). The authors thank Dietmar Leitner for assistance in NMR spectroscopic measurements, Arvid Soderhall and Jens Laettig for their help in molecular dynamics (MD) simulations, Viviane Uryga-Polowy for the MS measurements, and Daniel Geißler for helpful discussions. The structure of the AF6 PDZ domain is deposited in the protein data bank (PDB) under accession code 1XZ9 and the AF6 PDZ-5 f complex under accession code 2EXG. 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 Graphical Abstract In the groove: The “drugability” of protein–protein interaction domains is still a matter of debate. The 3D structure of a complex of a small organic ligand and the AF6 PDZ domain revealed the creation of a binding pocket by the ligand (see picture). The derived compound is able to compete with a natural peptide ligand of the domain and represents a basic building block for the generation of selective PDZ inhibitors. References 1T. Pawson, P. Nash, Science 2003, 300, 445– 452. 2Z. Songyang, A. S. Fanning, C. Fu, J. Xu, S. M. Marfatia, A. H. Chishti, A. Crompton, A. C. Chan, J. M. Anderson, L. C. Cantley, Science 1997, 275, 73– 77. 3B. Z. Harris, W. A. Lim, J. Cell Sci. 2001, 114, 3219– 3231. 4U. Wiedemann, P. Boisguerin, R. Leben, D. Leitner, G. Krause, K. Moelling, R. Volkmer-Engert, H. Oschkinat, J. Mol. Biol. 2004, 343, 703– 718. 5B. J. Hillier, K. S. Christopherson, K. E. Prehoda, D. S. Bredt, W. A. Lim, Science 1999, 284, 812– 815. 6D. A. 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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. Volume45, Issue23June 2, 2006Pages 3790-3795 ReferencesRelatedInformation
Publication Year: 2006
Publication Date: 2006-05-24
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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