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.

Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit / Hamley, I. W.; Brown, G. D.; Castelletto, V.; Cheng, G.; Venanzi, M.; Caruso, M.; Placidi, E.; Aleman, C.; Revilla-Lopez, G.; Zanuy, D.. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - 114:32(2010), pp. 10674-10683. [10.1021/jp105508g]

Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit

Placidi E.;
2010

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.
2010
Alanine; Amino Acid Sequence; Amyloid beta-Peptides; Circular Dichroism; Cryoelectron Microscopy; Hydrogels; Microscopy, Atomic Force; Models, Molecular; Molecular Dynamics Simulation; Molecular Structure; Peptides; Scattering, Small Angle; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Protein Structure, Secondary
01 Pubblicazione su rivista::01a Articolo in rivista
Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit / Hamley, I. W.; Brown, G. D.; Castelletto, V.; Cheng, G.; Venanzi, M.; Caruso, M.; Placidi, E.; Aleman, C.; Revilla-Lopez, G.; Zanuy, D.. - In: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL. - ISSN 1520-6106. - 114:32(2010), pp. 10674-10683. [10.1021/jp105508g]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1326853
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