title: Engineering amyloid-like assemblies from unstructured peptides via site-specific lipid conjugation.
abstract: Aggregation of amyloid beta (Aβ) into oligomers and fibrils is believed to play an important role in the development of Alzheimer's disease (AD). To gain further insight into the principles of aggregation, we have investigated the induction of β-sheet secondary conformation from disordered native peptide sequences through lipidation, in 1-2% hexafluoroisopropanol (HFIP) in phosphate buffered saline (PBS). Several parameters, such as type and number of lipid chains, peptide sequence, peptide length and net charge, were explored keeping the ratio peptide/HFIP constant. The resulting lipoconjugates were characterized by several physico-chemical techniques: Circular Dichroism (CD), Attenuated Total Reflection InfraRed (ATR-IR), Thioflavin T (ThT) fluorescence, Dynamic Light Scattering (DLS), solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy and Electron Microscopy (EM). Our data demonstrate the generation of β-sheet aggregates from numerous unstructured peptides under physiological pH, independent of the amino acid sequence. The amphiphilicity pattern and hydrophobicity of the scaffold were found to be key factors for their assembly into amyloid-like structures.
authors.affiliation: AC Immune SA, Lausanne, Switzerland.
authors.forename: María Pilar
authors.initials: MP
authors.lastname: López Deber
authors.affiliation: AC Immune SA, Lausanne, Switzerland.
authors.forename: David T
authors.initials: DT
authors.lastname: Hickman
authors.affiliation: Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nand
authors.affiliation: Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Baldus
authors.affiliation: AC Immune SA, Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfeifer
authors.affiliation: AC Immune SA, Lausanne, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Muhs
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D014867:Water