title: Influence of end-capping on the self-assembly of model amyloid peptide fragments.
abstract: The influence of charge and aromatic stacking interactions on the self-assembly of a series of four model amyloid peptides has been examined. The four model peptides are based on the KLVFF motif from the amyloid β peptide, Aβ(16-20) extended at the N terminus with two β-alanine residues. We have studied NH(2)-βAβAKLVFF-COOH (FF), NH(2)-βAβAKLVF-COOH (F), CH(3)CONH-βAβAKLVFF-CONH(2) (CapF), and CH(3)CONH-βAβAKLVFF-CONH(2) (CapFF). The former two are uncapped (net charge +2) and differ by one hydrophobic phenylalanine residue; the latter two are the analogous capped peptides (net charge +1). The self-assembly characteristics of these peptides are remarkably different and strongly dependent on concentration. NMR shows a shift from carboxylate to carboxylic acid forms upon increasing concentration. Saturation transfer measurements of solvent molecules indicate selective involvement of phenylalanine residues in driving the self-assembly process of CapFF due presumably to the effect of aromatic stacking interactions. FTIR spectroscopy reveals β-sheet features for the two peptides containing two phenylalanine residues but not the single phenylalanine residue, pointing again to the driving force for self-assembly. Circular dichroism (CD) in dilute solution reveals the polyproline II conformation, except for F which is disordered. We discuss the relationship of this observation to the significant pH shift observed for this peptide when compared the calculated value. Atomic force microscopy and cryogenic-TEM reveals the formation of twisted fibrils for CapFF, as previously also observed for FF. The influence of salt on the self-assembly of the model β-sheet forming capped peptide CapFF was investigated by FTIR. Cryo-TEM reveals that the extent of twisting decreases with increased salt concentration, leading to the formation of flat ribbon structures. These results highlight the important role of aggregation-induced pK(a) shifts in the self-assembly of model β-sheet peptides.
authors.affiliation: Department of Chemistry, University of Reading, Reading RG6 6AD, UK.
authors.forename: Valeria
authors.initials: V
authors.lastname: Castelletto
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hamley
authors.forename: Çelen
authors.initials: Ç
authors.lastname: Cenker
authors.forename: Ulf
authors.initials: U
authors.lastname: Olsson
authors.forename: Jozef
authors.initials: J
authors.lastname: Adamcik
authors.forename: Raffaele
authors.initials: R
authors.lastname: Mezzenga
authors.forename: Juan F
authors.initials: JF
authors.lastname: Miravet
authors.forename: Beatriu
authors.initials: B
authors.lastname: Escuder
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodríguez-Llansola
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry*; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D012965:Sodium Chloride / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012997:Solvents; C529399:amyloid beta-protein (16-20); D012965:Sodium Chloride