FTIR spectroscopic studies on aggregation process of the beta-amyloid 11-28 fragment and its variants

Aggregation of A beta peptides is a seminal event in Alzheimer's disease. Detailed understanding of the A beta# assembly process would facilitate the targeting and design of fibrillogenesis inhibitors. Here, conformational studies using FTIR spectroscopy are presented. As a model peptide, the 11-28 fragment of A beta was used. This model peptide is known to contain the core region responsible for A beta aggregation. The structural behavior of the peptide during aggregation provoked by the addition of water to A beta(11-28) solution in hexafluoroisopropanol was compared with the properties of its variants corresponding to natural, clinically relevant mutants at positions 21-23 (A21G, E22K, E22G, E22Q and D23N). The results showed that the aggregation of the peptides proceeds via a helical intermediate, and it is possible that the formation of et-helical structures is preceded by creation of 3(10)-helix/3(10)-turn structures. Copyright (c) 2008 European Peptide Society and John Wiley & Sons, Ltd.