PEGylated β‐Sheet Breaker Peptides as Inhibitors of β‐Amyloid Fibrillization

Abstract

Three PEGylated β-sheet breaker peptides are designed as new inhibitors of β-amyloid fibrillization. The peptide Ac-Leu–Pro–Phe–Phe–Asp-NH2, considered the lead compound, and hexamers in which taurine and β-alanine substitute the acetyl group, are conjugated to poly(ethylene glycol); this conjugates self-assemble into nanoparticles. The activity of the PEGylated peptides as inhibitors of amyloid fibrillization are tested in vitro using circular dichroism spectroscopy and scanning electron microscopy. The experimental results indicate that PEGylation does not impair the ability of the β-sheet breaker peptides to inhibit fibrillogenesis in vitro. Moreover, microscopy images of β-amyloid incubated for 6 days with the taurine-containing peptide, suggest that this conjugate has major anti-fibrillogenesis activity and demonstrate the important role of the sulfonamide function against the amyloid aggregation

Bioinspired synthetic polymers-based inhibitors of Alzheimer's amyloid-β peptide aggregation

“…Scipioni and co-workers investigated the fibrillogenesis-inhibiting activity of PEGylated conjugates of the different peptide derivates related to the above β-sheet breaker pentapeptide iAβ 5 . 140 Conjugation was carried out by using PEG with a lower MW of 2 kDa to afford new hybrid amphiphilic conjugates: acetyl protected Ac-LPFFD(mPEG)-NH 2 (Ac-iAβ 5 -PEG), β-alanine containing H-βAla-LPFFD(mPEG)-NH 2 (βAla-iAβ 5 -PEG), and taurine containing H-Tau-LPFFD(mPEG)-NH 2 (Tau-iAβ 5 -PEG) (Fig. 13A–C), which self-assembled in core–shell nanoparticles morphology with PEGylated outer surface to protect the peptide from enzymatic proteolysis in the biological environment.…”