title: Inhibition of amyloid aggregation by formation of helical assemblies.
abstract: The formation of amyloid aggregates is responsible for a wide range of diseases, including Alzheimer's and Parkinson's disease. Although the amyloid-forming proteins have different structures and sequences, all undergo a conformational change to form amyloid aggregates that have a characteristic cross-β-structure. The mechanistic details of this process are poorly understood, but different strategies for the development of inhibitors of amyloid formation have been proposed. In most cases, chemically diverse compounds bind to an elongated form of the protein in a β-strand conformation and thereby exert their therapeutic effect. However, this approach could favor the formation of prefibrillar oligomeric species, which are thought to be toxic. Herein, we report an alternative approach in which a helical coiled-coil-based inhibitor peptide has been designed to engage a coiled-coil-based amyloid-forming model peptide in a stable coiled-coil arrangement, thereby preventing rearrangement into a β-sheet conformation and the subsequent formation of amyloid-like fibrils. Moreover, we show that the helix-forming peptide is able to disassemble mature amyloid-like fibrils.
authors: Institut für Chemie und Biochemie, Freie Universität Berlin, Germany.
authors: Enrico
authors: E
authors: Brandenburg
authors: Hans
authors: H
authors: von Berlepsch
authors: Ulla I M
authors: UI
authors: Gerling
authors: Christoph
authors: C
authors: Böttcher
authors: Beate
authors: B
authors: Koksch
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002942:Circular Dichroism; D003198:Computer Simulation; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D010455:Peptides