Amino-Acid Based Enantioselective Nanoparticles for Inhibition of Amyloid Fibrillation

Amyloidoses are family of diseases characterized by abnormal protein folding and aggregation, for which a search for cure is still investigated. Inhibition of protein aggregation was previously demonstrated for therapeutic benefits.

Many small molecules and short peptides were evaluated as inhibitors of amyloid aggregation. A possible strategy towards inhibition is using nanoparticles, which carry advantageous characteristics such as improved biological stability, ease of delivery and structural specificity.

Herein we report on lysine based carbon quantum dots, containing either D or L enantiomer, inhibition of Prion peptide (PrP, 106-126 sequence) fibril assembly and plaque formation, acting as a novel class of chiral amyloid inhibitor. The L enantiomer carbon dots showed major fibrillation inhibition, compared with the D-enantiomer. Thus, it seems that the Lysine carbon dot interaction with the PrP is highly stereoselective. This inhibitory effect was demonstrated using multiple fibril morphology imaging techniques, peptides secondary structure analysis and other biophysical approaches.

This is the first report of enantioselective inhibition of PrP aggregation using chiral nanoparticles. The work provides new insights into chiral nanoparticles and peptide interactions, and sheds light on wide possibilities of amyloid inhibition using chiral carbon-based nanostructures.