Amyloid-forming propensity of the hydrophobic non-natural amino acid on the fibril-forming core peptide of human tau

Amino acid residues with aromatic side chains, such as Tyr and Phe, are known to play essential roles in forming and stabilizing the amyloid fibrils of pathogenic polypeptides by affecting their amyloid forming propensity. We have studied the amyloid-type aggregation of peptides containing non-natural amino acid derived from a core part of human pathogenic protein, tau. The hydrophobic nature of the biphenyl group and its intermolecular aromatic interactions strongly alter their amyloid formation properties.

TEM images of amyloid-type fibers formed from PHF6 (left) and phenyl-substituted PHF6FPh (right). Scale bar: 100 nm. The tyrosine residue (Y) corresponds to the native Tyr-310 residue of tau.Figure optionsDownload as PowerPoint slide