Abstract
α-Synuclein forms amyloid deposits in the dopaminergic neurons; a process that is believed to contribute to the Parkinson’s disease. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation share common physic-chemical features and exert their effects by common modes. This prompted the idea that molecules able to inhibit a protein aggregation process may cross-react with other amyloidogenic proteins, interfering in their fibrils formation. We investigate the ability of analogues of the heptapeptide H-Arg-Lys-Val-MePhe-Tyr-Thr-Trp- OH2, an inhibitor of Aβ-peptide aggregation, to cross-react with α-synuclein interfering with its fibril formation. The influence of the MePhe topography on the interaction with α-synuclein has also been evaluated, replacing the MePhe residue with either Phe or the conformationally restricted Tic residues. Peptides interact with good affinity with the
Keywords: α-synuclein, β-breaker peptides, conformational constraints, protein-peptide interaction.
Protein & Peptide Letters
Title:Peptides as Modulators of α-Synuclein Aggregation
Volume: 22 Issue: 4
Author(s): Paolo Ruzza, Matteo Gazziero, Maria De Marchi, Giada Massalongo, Anna Marchiani, Ida Autiero, Isabella Tessari, Luigi Bubacco and Andrea Cald
Affiliation:
Keywords: α-synuclein, β-breaker peptides, conformational constraints, protein-peptide interaction.
Abstract: α-Synuclein forms amyloid deposits in the dopaminergic neurons; a process that is believed to contribute to the Parkinson’s disease. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation share common physic-chemical features and exert their effects by common modes. This prompted the idea that molecules able to inhibit a protein aggregation process may cross-react with other amyloidogenic proteins, interfering in their fibrils formation. We investigate the ability of analogues of the heptapeptide H-Arg-Lys-Val-MePhe-Tyr-Thr-Trp- OH2, an inhibitor of Aβ-peptide aggregation, to cross-react with α-synuclein interfering with its fibril formation. The influence of the MePhe topography on the interaction with α-synuclein has also been evaluated, replacing the MePhe residue with either Phe or the conformationally restricted Tic residues. Peptides interact with good affinity with the
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Ruzza Paolo, Gazziero Matteo, De Marchi Maria, Massalongo Giada, Marchiani Anna, Autiero Ida, Tessari Isabella, Bubacco Luigi and Cald Andrea, Peptides as Modulators of α-Synuclein Aggregation, Protein & Peptide Letters 2015; 22 (4) . https://dx.doi.org/10.2174/0929866522666150209142649
DOI https://dx.doi.org/10.2174/0929866522666150209142649 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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