title: Altering peptide fibrillization by polymer conjugation.
abstract: A strategy is presented that exploits the ability of synthetic polymers of different nature to disturb the strong self-assembly capabilities of amyloid based β-sheet forming peptides. Following a convergent approach, the peptides of interest were synthesized via solid-phase peptide synthesis (SPPS) and the polymers via reversible addition-fragmentation chain transfer (RAFT) polymerization, followed by a copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) to generate the desired peptide-polymer conjugates. This study focuses on a modified version of the core sequence of the β-amyloid peptide (Aβ), Aβ(16-20) (KLVFF). The influence of attaching short poly(N-isopropylacrylamide) and poly(hydroxyethylacrylate) to the peptide sequences on the self-assembly properties of the hybrid materials were studied via infrared spectroscopy, TEM, circular dichroism and SAXS. The findings indicate that attaching these polymers disturbs the strong self-assembly properties of the biomolecules to a certain degree and permits to influence the aggregation of the peptides based on their β-sheets forming abilities. This study presents an innovative route toward targeted and controlled assembly of amyloid-like fibers to drive the formation of polymeric nanomaterials.
authors: Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney, NSW, 2006, Australia.
authors: Sabrina
authors: S
authors: Dehn
authors: Valeria
authors: V
authors: Castelletto
authors: Ian W
authors: IW
authors: Hamley
authors: Sébastien
authors: S
authors: Perrier
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000179:Acrylates / Q000737:chemistry*; D000180:Acrylic Resins; D000480:Alkynes / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D002942:Circular Dichroism; D061565:Cycloaddition Reaction; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D017433:Protein Structure, Secondary; D053838:Scattering, Small Angle; D060327:Solid-Phase Synthesis Techniques; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000178:Acrylamides; D000179:Acrylates; D000180:Acrylic Resins; D000480:Alkynes; D016229:Amyloid beta-Peptides; D001386:Azides; D010446:Peptide Fragments; D011108:Polymers; D012996:Solutions; C529399:amyloid beta-protein (16-20); C052970:poly-N-isopropylacrylamide; C035957:2-hydroxyethyl acrylate