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

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-beta (A beta) variants. To inhibit these toxic processes, we synthesized antioxidant-conjugated peptides comprised of Trolox and various C-terminal motifs of Ab variants, TxA beta(x-n) (x = 34, 36, 38, 40; n = 40, 42, 43). Most of these compounds were found to exhibit anti-aggregation activities. Among them, TxA beta(36-42) significantly inhibited A beta(1-42) aggregation, showed potent antioxidant activity, and protected SH-SY5Y cells from A beta(1-42)-induced cytotoxicity. Thus, this method represents a promising strategy for developing multifunctional AD therapeutic agents. (C) 2016 Elsevier Ltd. All rights reserved.