Design, synthesis, and evaluation of Trolox-conjugated amyloid-β C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer's disease.

Abstract Two hallmarks of Alzheimer’s disease (AD) observed in the brains of patients with the disease include oxidative injury and deposition of protein aggregates comprised of amyloid-β (Aβ) variants. To inhibit these toxic processes, we synthesized antioxidant-conjugated peptides comprised of Trolox and various C-terminal motifs of Aβ variants, TxAβ x – n ( x  = 34, 36, 38, 40; n  = 40, 42, 43). Most of these compounds were found to exhibit anti-aggregation activities. Among them, TxAβ 36–42 significantly inhibited Aβ 1–42 aggregation, showed potent antioxidant activity, and protected SH-SY5Y cells from Aβ 1–42 -induced cytotoxicity. Thus, this method represents a promising strategy for developing multifunctional AD therapeutic agents.