Design, synthesis, and evaluation of Trolox-conjugated amyloid-ß C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer's disease.
Bioorg Med Chem
; 24(18): 4138-4143, 2016 09 15.
Article
em En
| MEDLINE
| ID: mdl-27407032
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-ß (Aß) variants. To inhibit these toxic processes, we synthesized antioxidant-conjugated peptides comprised of Trolox and various C-terminal motifs of Aß variants, TxAßx-n (x=34, 36, 38, 40; n=40, 42, 43). Most of these compounds were found to exhibit anti-aggregation activities. Among them, TxAß36-42 significantly inhibited Aß1-42 aggregation, showed potent antioxidant activity, and protected SH-SY5Y cells from Aß1-42-induced cytotoxicity. Thus, this method represents a promising strategy for developing multifunctional AD therapeutic agents.
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MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Cromanos
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Doença de Alzheimer
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Agregados Proteicos
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Antioxidantes
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article