title: Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit.
abstract: The self-assembly of a peptide based on a sequence from the amyloid beta peptide but incorporating the non-natural amino acid beta-2-thienylalanine (2-Thi) has been investigated in aqueous and methanol solutions. The peptide AAKLVFF was used as a design motif, replacing the phenylalanine residues (F) with 2-Thi units to yield (2-Thi)(2-Thi)VLKAA. The 2-Thi residues are expected to confer interesting electronic properties due to charge delocalization and pi-stacking. The peptide is shown to form beta-sheet-rich amyloid fibrils with a twisted morphology, in both water and methanol solutions at sufficiently high concentration. The formation of a self-assembling hydrogel is observed at high concentration. Detailed molecular modeling using molecular dynamics methods was performed using NOE constraints provided by 2D-NMR experiments. The conformational and charge properties of 2-Thi were modeled using quantum mechanical methods, and found to be similar to those previously reported for the beta-3-thienylalanine analogue. The molecular dynamics simulations reveal well-defined folded structures (turn-like) in dilute aqueous solution, driven by self-assembly of the hydrophobic aromatic units, with charged lysine groups exposed to water.
authors.affiliation: School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, UK.
authors.forename: I W
authors.initials: IW
authors.lastname: Hamley
authors.forename: G D
authors.initials: GD
authors.lastname: Brown
authors.forename: V
authors.initials: V
authors.lastname: Castelletto
authors.forename: G
authors.initials: G
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Venanzi
authors.forename: M
authors.initials: M
authors.lastname: Caruso
authors.forename: E
authors.initials: E
authors.lastname: Placidi
authors.forename: C
authors.initials: C
authors.lastname: Aleman
authors.forename: G
authors.initials: G
authors.lastname: Revilla-López
authors.forename: D
authors.initials: D
authors.lastname: Zanuy
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics; D002942:Circular Dichroism; D020285:Cryoelectron Microscopy; D020100:Hydrogels / Q000737:chemistry; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D053838:Scattering, Small Angle; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D016229:Amyloid beta-Peptides; D020100:Hydrogels; D010455:Peptides; C100177:2-thienylalanine; D000409:Alanine