(570a) Engineering a Self-Assembling Peptide System Derived from Beta-Amyloid

The misfolding of beta-amyloid protein leads to neurotoxic aggregation in the brain. Amyloid fibrils and neurofibrillary tangles in the brain are hallmarks of Alzheimer’s disease progression. The driving force of aggregation of the 40 or 42 residue peptide is an internal domain of seven residues known as the hydrophobic central domain. Our group has developed a novel, self-assembling, dual peptide system derived from this sequence. The novel peptides do not homo-assemble in solution, although rapid hetero-assembly occurs upon mixing. The resulting aggregates have been characterized extensively, including positive ThT fluorescence and beta-sheet secondary structure typical of amyloid aggregates. Beta-sheet composition and morphology can be altered with varying salt concentrations in the buffer and the addition of terminal capping groups. This system has useful applications in the development of novel functional biomaterials, as well as applications in identifying the mechanisms of amyloid toxicity in neurodegenerative diseases such as Alzheimer’s disease.