A Ferrocene-Tagged Amyloid-b Fragment for Rapid Screening of Aggregation Inhibitors from Natural Compounds by HPLCElectrochemical Detection

摘要

Aggregates of amyloid beta (Aβ) peptides are believed to be responsible for the neuropathology of Alzheimer's disease. In this work, ferrocene (Fc) is attached to the aggregating core of the Aβ peptides, KLVFFAE. Inhibition of Fc-KLVFFAE aggregation by curcumin, a natural compound, was monitored by HPLC-electrochemical detection (HPLC-EC). The Fc oxidation current is dependent on the incubation condition and curcumin can retain Fc- KLVFFAE in its monomeric form. We demonstrate that tagging Fc to KLVFFAE affords a cost-effective and electroactive mimicry of Aβ(1-42) and HPLC-EC is suitable for sensitive, reproducible, and facile screening of drugs for inhibiting the aggregation of Aβ peptides.