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
Keywords: α-synuclein, β-breaker peptides, conformational constraints, protein-peptide interaction.
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