α-Aminoisobutyric acid modified protected analogues of β-amyloid residue 17–20: a change from sheet to helix

Abstract

The strong intermolecular interactions mediated by short hydrophobic sequences (e.g., 17–20, -l-Leu-l-Val-l-Phe-l-Phe-) in the middle of Aβ are known to play a crucial role in the neuropathology of Alzheimer's disease. FTIR, TEM and Congo red binding studies indicated that a series of l-Ala substituted terminally protected peptides related to the sequence 17–20 of the β-amyloid peptide, adopted β-sheet conformations. However, the Aib-modified analogues disrupt the β-sheet structure and switch over to a 310 helix with increasing number of Aib residues. X-ray crystallography shed some light on the change from sheet to helix at atomic resolution.