Inhibition of human prion neuropeptide PrP106-126 aggregation by hexacoordinated ruthenium complexes

• Ru complexes of various molecular configurations were employed for this study.
• The Ru complexes could bind to PrP106–126 and inhibit its aggregation behavior.
• Metal coordination and hydrophobic interaction contributed to the binding affinity.
• The Ru-based aromatic complexes displayed better inhibitory effects.
• The study paved the way for potential Ru-based metallodrugs against prion diseases.

Prion disease is a neurodegenerative disorder that can occur among humans and other animals. The aberrant isoform of prion protein PrPSc has been identified as the infectious agent. The neuropeptide PrP106-126 has been widely used as a suitable model to study the biological and physiochemical properties of PrPSc. PrP106-126 shares several physicochemical and biological properties with PrPSc, including cellular toxicity, fibrillogenesis, and membrane-binding affinity. Ruthenium complexes are commonly employed in anti-cancer studies due to their low cellular toxicity. In this study, six hexacoordinated ruthenium complexes with different molecular configurations were used to investigate their effects on PrP106-126 aggregation inhibition. Results revealed that the interaction between the complexes and the peptide included metal coordination and hydrophobic interaction mainly. Those complexes with aromatic structure displayed better inhibitory effects, although they only had a common binding affinity to PrP106-126. This study provided better understanding on the interaction of metal complexes with PrP106-126 and paved the way for potential Ru-based metallodrugs against prion diseases.

Fibrils and spherical like aggregates of PrP106-126 are disaggregated after incubating with ruthenium complexes. Further, the interactions of ruthenium complexes with prion neuropeptide are based on metal coordination and hydrophobic interaction predominantly.Figure optionsDownload as PowerPoint slide