Discrete conformational changes as regulators of the hydrolytic properties of beta‐amyloid (1–40)

摘要: Beta-amyloid (1–40) (Abeta), the main component of senile plaques seen in brains Alzheimer's disease patients, was found to be toxic both as fibrils and smaller soluble globular aggregates. The hydrolytic properties Abeta, a new biochemical activity described previously [Brzyska M, Bacia A & Elbaum D (2001) Eur J Biochem268, 3443–3454], may contribute its overall toxicity. In this study, hydrolysis fluorescein ester series studied under predetermined conditions affecting Abeta hydrophobicity conformation. Reaction products most effectively decomposed (dibutyrate) were characterized using HPLC ESI-MS. Hydrophobicity measured by bis-8-anilinonaphthalene fluorescence, correlated with abilities. FTIR CD data analysis showed relationship between enhanced abilities structure. Seriously limited caused higher peptide concentrations is consistent monomeric/dimeric species participation process, confirmed thioflavine T binding. Inhibition β-sheet breaker (LPFFD), indicating that central hydrophobic cluster (amino acids 17–21) participates process. reported suggest small conformational alterations structure have pronounced effect on functions biological activity.