Lysine‐Derived Carbon Dots for Chiral Inhibition of Prion Peptide Fibril Assembly. Issue 4 (28th May 2018)

• Record Type: Journal Article
• Authors: Arad, Elad; Bhunia, Susanta Kumar; Jopp, Jürgen; Kolusheva, Sofiya; Rapaport, Hanna; Jelinek, Raz
• Is Part Of: Advanced therapeutics. Volume 1:Issue 4(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-05-28
• Subjects: amyloid diseases -- amyloid inhibitors -- carbon dots -- chiral nanoparticles -- prion protein; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.201800006
• Languages: English
• ISSNs: 2366-3987

Abstract

Abstract: The transmissible spongiform encephalopathies are a family of diseases characterized by abnormal folding and aggregation of the prion protein. One of the directions in the search for cure for these and other amyloid diseases focuses on the inhibition of protein aggregation by small molecules, short peptides, and nanoparticles. Nanoparticles seem to be particularly promising therapeutic candidates since they are stable, can be made biocompatible, and might readily traverse physiological barriers such as the blood–brain barrier. Here, a novel class of chiral amyloid inhibitors consisting of carbon quantum dots (C‐dots) that are synthesized from eitherd ‐ orl‐ lysine (Lys) as the sole carbonaceous building block are reported. The interactions of the chiral lys‐C‐dots with the amyloidogenic determinant of the prion peptide (PrP, 106–126 sequence) in the presence of lipid bilayers appears to be highly stereoselective, with thel ‐Lys‐C‐dots being superior to thed ‐Lys‐C‐dots in their ability to modulate the structural transformations and aggregation of PrP(106–126). This work provides new insights into chiral effects upon amyloid peptides and opens the way to developing chiral carbon‐based nanostructures as advanced amyloid inhibitors. Abstract : Enantiomeric carbon dots prepared froml ‐lysine ord ‐Lysine as the sole carbonaceous source exhibit dramatic chiral modulation of bilayer‐induced aggregation of PrP(106–126), the amyloidogenic determinant of the prion protein. Distinct enantiomer‐dependent effects upon peptide conformations and fibril morphologies are recorded. This work points to a potential therapeutic route for combating protein misfolding diseases through chiral interactions of carbon nanomaterials.