Authors: Arai, Takuya; Ohno, Akiko; Kazunori, Mori; Kakizawa, Taeko; Kuwata, Hiroshi; Ozawa, Toshihiko; Shibanuma, Motoko; Hara, Shuntaro; Ishida, Seiichi; Kurihara, Masaaki; Miyata, Naoki; Nakagawa, Hidehiko; Fukuhara, Kiyoshi; Bioorganic & Medicinal Chemistry; (2016); 10.1016/j.bmc.2016.06.057
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-? (A?) variants. To inhibit these toxic processes, we synthesized antioxidant-conjugated peptides comprised of Trolox and various C-terminal motifs of A? variants, TxA?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?36-42 significantly inhibited A?1-42 aggregation, showed potent antioxidant activity, and protected SH-SY5Y cells from A?1-42-induced cytotoxicity. Thus, this method represents a promising strategy for developing multifunctional AD therapeutic agents.