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

Prion disease is a neurodegenerative disorder that can occur among humans and other animals. The aberrant isoform of prion protein PrP(Sc) 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 PrP(Sc). PrP106-126 shares several physicochemical and biological properties with PrP(Sc), 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.