PEGylated β‐Sheet Breaker Peptides as Inhibitors of β‐Amyloid Fibrillization. Issue 2 (30th November 2016)

• Record Type: Journal Article
• Authors: De Santis, Serena; Chiaraluce, Roberta; Consalvi, Valerio; Novelli, Federica; Petrosino, Maria; Punzi, Pasqualina; Sciubba, Fabio; Giordano, Cesare; Masci, Giancarlo; Scipioni, Anita
• Is Part Of: ChemPlusChem. Volume 82:Issue 2(2017)
• Page Start: 241
• Page End: 250
• Publication Date: 2016-11-30
• Subjects: beta-sheet breaker peptides -- hybrid peptide conjugates -- nanoparticles -- PEGylation -- self-assembly; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201600550
• Languages: English
• ISSNs: 2192-6506

Abstract

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. Abstract : PEGylated β‐sheet breaker peptides : the PEGylated peptides H‐Tau–Leu–Pro–Phe–Phe–Asp‐NH2 (Tau‐PEP5 ‐PEG) and H‐β‐Ala–Leu–Pro–Phe–Phe–Asp‐NH2 self‐assemble into nanoparticles capable of inhibiting β‐amyloid fibrillization. PEGylation does not affect the anti‐fibrillogenesis activity of the peptides in vitro. Importantly, electron micrographs of β‐amyloid incubated with the taurine‐containing conjugate for up to six days does not show fibrils, proving the important role of the sulfonamide function against the amyloid aggregation (see figure).