Selectively N-Methylated Soluble IAPP Mimics as Potent IAPP Receptor Agonists and Nanomolar Inhibitors of Cytotoxic Self-Assembly of Both IAPP and Aβ40†
Dr. Li-Mei Yan
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDr. Aleksandra Velkova
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDipl.-Chem. Marianna Tatarek-Nossol
Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen (Germany)
Search for more papers by this authorProf. Dr. Gerhard Rammes
Department of Anesthesiology, Technische Universität München, Klinikum Rechts der Isar, Ismaninger Strasse 22, 81675 München (Germany)
Search for more papers by this authorDr. Andrei Sibaev
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorDr. Erika Andreetto
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDipl.-Ing. Michael Kracklauer
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDipl.-Biochem. Maria Bakou
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen (Germany)
Search for more papers by this authorDipl.-Chem. Eleni Malideli
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorProf. Dr. Burkhard Göke
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorProf. Dr. Jörg Schirra
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorProf. Dr. Martin Storr
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorCorresponding Author
Prof. Dr. Aphrodite Kapurniotu
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/Search for more papers by this authorDr. Li-Mei Yan
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDr. Aleksandra Velkova
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDipl.-Chem. Marianna Tatarek-Nossol
Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen (Germany)
Search for more papers by this authorProf. Dr. Gerhard Rammes
Department of Anesthesiology, Technische Universität München, Klinikum Rechts der Isar, Ismaninger Strasse 22, 81675 München (Germany)
Search for more papers by this authorDr. Andrei Sibaev
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorDr. Erika Andreetto
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDipl.-Ing. Michael Kracklauer
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorDipl.-Biochem. Maria Bakou
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen (Germany)
Search for more papers by this authorDipl.-Chem. Eleni Malideli
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Search for more papers by this authorProf. Dr. Burkhard Göke
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorProf. Dr. Jörg Schirra
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorProf. Dr. Martin Storr
Medizinische Klinik und Poliklinik II, Klinikum der Universität München-Großhadern, Marchioninistrasse 15, 81377 München (Germany)
Search for more papers by this authorCorresponding Author
Prof. Dr. Aphrodite Kapurniotu
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/
Division of Peptide Biochemistry, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising (Germany) http://pbch.wzw.tum.de/Search for more papers by this authorWe thank A. Kazantzis for peptide synthesis, A. Kastenmüller and S. Weinkauf for help with TEM, and J. Bernhagen for helpful discussions. This work was supported by the Deutsche Forschungsgemeinschaft (DFG). IAPP=islet amyloid polypeptide.
Graphical Abstract
The selective incorporation of N-methyl groups in the highly amyloidogenic and cytotoxic sequence of the type 2 diabetes islet amyloid polypeptide (IAPP) generates a unique class of soluble and nontoxic IAPP mimics. These polypeptides combine potent IAPP receptor agonism with nanomolar-affinity inhibitory potential on the amyloid formation and cell-damaging effects of both IAPP and the Alzheimer's β-amyloid peptide (Aβ40).
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