Self-Assembly of a Designed Amyloid Peptide Containing the Functional Thienylalanine Unit
Tipus de documentArticle
Condicions d'accésAccés restringit per política de l'editorial
The self-assembly of a peptide based on a sequence from the amyloid peptide but incorporating the nonnatural amino acid -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 π-stacking. The peptide is shown to form -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 -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.
CitacióHamley, . [et al.]. Self-Assembly of a Designed Amyloid Peptide Containing the Functional Thienylalanine Unit. "Journal of physical chemistry B", 19 Agost 2010, vol. 114, núm. 32, p. 10674-10683.
Versió de l'editorwww.ncbi.nlm.nih.gov/pubmed/20662537