Small-Molecule Inhibitors of Islet Amyloid Polypeptide Fibril Formation†
Rajesh Mishra Dr.
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorBruno Bulic Dr.
Max-Planck-Institute for Molecular Physiology, Department of Chemical Biology, and Center for Applied Chemical Genomics, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
Search for more papers by this authorDaniel Sellin
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorSuman Jha
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorHerbert Waldmann Prof. Dr.
Max-Planck-Institute for Molecular Physiology, Department of Chemical Biology, and Center for Applied Chemical Genomics, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
Search for more papers by this authorRoland Winter Prof. Dr.
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorRajesh Mishra Dr.
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorBruno Bulic Dr.
Max-Planck-Institute for Molecular Physiology, Department of Chemical Biology, and Center for Applied Chemical Genomics, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
Search for more papers by this authorDaniel Sellin
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorSuman Jha
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorHerbert Waldmann Prof. Dr.
Max-Planck-Institute for Molecular Physiology, Department of Chemical Biology, and Center for Applied Chemical Genomics, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany
Search for more papers by this authorRoland Winter Prof. Dr.
Faculty of Chemistry, Physical Chemistry I—Biophysical Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany, Fax. (+49) 231-755-3901
Search for more papers by this authorFinancial support from the DFG, the Fonds der Chemischen Industrie, the country NRW and the EU (Europäischer Fonds für regionale Entwicklung) is gratefully acknowledged.
Graphical Abstract
Small and effective: The pathological aggregation of amylin (IAPP), which leads to type II diabetes mellitus, is effectively inhibited by small-molecule rhodanine-based inhibitors at nanomolar concentrations. The prevention of aggregation by treatment with the inhibitor is demonstrated by AFM (see image).
Supporting Information
Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705372_s.pdf or from the author.
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References
- 1C. M. Dobson, Nature 2003, 426, 884–890.
- 2M. R. Nilsson, Methods 2004, 34, 151–160.
- 3F. Chiti, C. M. Dobson, Annu. Rev. Biochem. 2006, 75, 333–366.
- 4P. Westermark, C. Wernstedt, E. Wilander, D. W. Hayden, T. D. O'Brien, K. H. Johnson, Proc. Natl. Acad. Sci. USA 1987, 84, 3881–3885.
- 5G. J. Cooper, A. C. Willis, A. Clark, R. C. Turner, R. B. Sim, K. B. Reid, Proc. Natl. Acad. Sci. USA 1987, 84, 8628–8632.
- 6K. H. Johnson, T. D. O'Brien, C. Betsholtz, P. Westermark, Lab. Invest. 1992, 66, 522–535.
- 7M. F. M. Engel, H. Yigittop, R. C. Elgersma, D. T. S Rijkers, R. M. J. Liskamp, B. Kruijff, J. W. M. Höppener, J. A. Killian, J. Mol. Biol. 2006, 356, 783–789.
- 8D. H. J. Lopes, A. Meister, A. Gohlke, A. Hauser, A. Blume, R. Winter, Biophys. J. 2007, 93, 3132–3141.
- 9J. W. Höppener, B. Ahrén, C. J. Lips, N. Engl. J. Med. 2000, 343, 411–419.
- 10C. Y. Lin, T. Gurlo, R. Kayed, A. E. Butler, L. Haataja, C. G. Glabe, P. C. Butler, Diabetes 2007, 56, 1324–1332.
- 11P. Westermark, U. Engström, K. H. Johnson, G. T. Westermark, C. Betsholtz, Proc. Natl. Acad. Sci. USA 1990, 87, 5036–5040.
- 12L. M. Yan, M. Tatarek-Nossol, A. Velkova, A. Kazantzis, A. Kapurniotu, Proc. Natl. Acad. Sci. USA 2006, 103, 2046–2051.
- 13L. M. Yan, A. Velkova, M. Tatarek-Nossol, E. Andreetto, A. Kapurniotu, Angew. Chem. 2007, 119, 1268–1274; Angew. Chem. Int. Ed. 2007, 46, 1246–1252.
- 14F. E. Cohen, J. W. Kelly, Nature 2003, 426, 905–909.
- 15Y. Porat, A. Abramowitz, E. Gazit, Chem. Biol. Drug Des. 2006, 67, 27–37.
- 16C. Adessi, C. Soto, Curr. Med. Chem. 2002, 9, 963–978.
- 17M. Necula, R. Kayed, S. Milton, C. G. Glabe, J. Biol. Chem. 2007, 282, 10311–10324.
- 18M. Bartolini, C. Bertucci, M. L. Bolognesi, A. Cavalli, C. Melchiorre, V. Andrisano, ChemBioChem 2007, 8, 2152–2161.
- 19M. Pickhardt, Z. Gazova, M. von Bergen, I. Khlistunova, Y. Wang, A. Hascher, E. M. Mandelkow, J. Biernat, E. Mandelkow, J. Biol. Chem. 2005, 280, 3628–3635.
- 20M. Pickhardt, G. Larbig, I. Khlistunova, A. Coksezen, B. Meyer, E. M. Mandelkow, B. Schmidt, E. Mandelkow, Biochemistry 2007, 46, 10016–10023.
- 21B. Bulic, M. Pickhardt, I. Khlistunova, J. Biernat, E. M. Mandelkow, E. Mandelkow, H. Waldmann, Angew. Chem. 2007, 119, 9375–9379;
10.1002/ange.200704051 Google ScholarAngew. Chem. Int. Ed. 2007, 46, 9215–9219.
- 22E. Zeiger, B. Anderson, S. Haworth, T. Lawlor, K. Mortelmans, W. Speck, Environ. Mutagen. 1987, 9, 1–109.
- 23C. Chirita, M. Necula, J. Kuret, Biochemistry 2004, 43, 2879–2887.
- 24S. Taniguchi, N. Suzuki, M. Masuda, S. Hisanaga, T. Iwatsubo, M. Goedert, M. Hasegawa, J. Biol. Chem. 2005, 280, 7614–7623.
- 25R. Jansen, W. Dzwolak, R. Winter, Biophys. J. 2005, 88, 1344–1353.
- 26J. D. Knight, A. D. Miranker, J. Mol. Biol. 2004, 341, 1175–1187.
- 27S. A. Jayasinghe, R. Langen, Biochim. Biophys. Acta 2007, 1768, 2002–2009.
- 28S. A. Tatulian, Biophys. J. 2001, 80, 789–800.
- 29W. Dzwolak, V. Smirnovas, R. Jansen, R. Winter, Protein Sci. 2004, 13, 1927–1932.
- 30R. Kayed, E. Head, J. L. Thompson, T. M. McIntire, S. C. Milton, C. W. Cotman, C. G. Glabe, Science 2003, 300, 486–489.
