A Peptide Hairpin Inhibitor of Amyloid β-Protein Oligomerization and Fibrillogenesis

Amylold beta-protein (A beta) self-assembly is linked strongly to Alzheimer's disease. We found that PP-Leu, a tridecapeptide analogue of broad-spectrum antiviral peptides termed theta-defensins, potently inhibits A beta oligomer and fibril Formation. This effect appeared to be mediated through sequestration of the amyloidogenic A beta peptide in colloid-like assemblies. PP-Leu comprises a turn formed by a D-Pro-L-Pro amino acid dyad and stabilized by a disulfide bond, a motif that was exceptionally resistant to endoproteinase K digestion, This combination of assembly inhibitory activity and protease resistance Suggests that PP-Leu may have potential therapeutic value.