Tetrapeptidic molecular hydrogels: self-assembly and co-aggregation with amyloid fragment Aβ1-40.

A new family of isomeric tetrapeptides containing aromatic and polar amino acid residues that are able to form molecular hydrogels following a smooth change in pH is described. The hydrogels have been studied by spectroscopic and microscopic techniques showing that the peptide primary sequence has an enormous influence on the self-assembly process. In particular, the formation of extended hydrophobic regions and the appearance of π-stacking interactions have been revealed as the driving forces for aggregation. Moreover, the interaction of these compounds with amyloid peptidic fragment Aβ1-40 has been studied and some of them have been shown to act as templates for the aggregation of this peptide into non-β-sheet fibrillar structures. These compounds could potentially be used for the capture of toxic, soluble amyloid oligomers.