Pseudopeptide Designed to Inhibit Oligomerization and Redox Chemistry in Alzheimer’s Disease

Aggregation of amyloid beta peptide (Aβ) and inflammatory processes associated with the generation of superoxide, hydrogen peroxide, and hydroxyl radicals are responsible for neurotoxicity in Alzheimer’s disease. The latter are a result of the redox activity of copper-bound Aβ complexes with molecular oxygen. A ligand (PI1), previously designed to compete with Aβ for copper, and a pseudopeptide (SGC1) with a property of breaking the self-aggregation of Aβ, are attached to each other to form a new pseudopeptide (TGC1) in this study. Using a combination of density functional theory and molecular dynamics simulations, we show that TGC1 should have the ability to inhibit self-aggregation of Aβ, prevent the binding of copper to Aβ, and quench the redox activity of the copper. This trifunctional ligand is a good candidate for development into an anti-Alzheimer drug.