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-López, G. and Zanuy, D. (2010) Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit. Journal of Physical Chemistry B, 114 (32). pp. 10674-10683. ISSN 1520-6106
Full text not archived in this repository.
To link to this article DOI: 10.1021/jp105508g
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.
Repository Staff Only: item control page