Unimolecular Chemiexcited Oxygenation of Pathogenic Amyloids.
Angew Chem Int Ed Engl
; 63(31): e202405605, 2024 07 29.
Article
em En
| MEDLINE
| ID: mdl-38757875
ABSTRACT
Pathogenic protein aggregates, called amyloids, are etiologically relevant to various diseases, including neurodegenerative Alzheimer disease. Catalytic photooxygenation of amyloids, such as amyloid-ß (Aß), reduces their toxicity; however, the requirement for light irradiation may limit its utility in large animals, including humans, due to the low tissue permeability of light. Here, we report that Cypridina luciferin analogs, dmCLA-Cl and dmCLA-Br, promoted selective oxygenation of amyloids through chemiexcitation without external light irradiation. Further structural optimization of dmCLA-Cl led to the identification of a derivative with a polar carboxylate functional group and low cellular toxicity dmCLA-Cl-acid. dmCLA-Cl-acid promoted oxygenation of Aß amyloid and reduced its cellular toxicity without photoirradiation. The chemiexcited oxygenation developed in this study may be an effective approach to neutralizing the toxicity of amyloids, which can accumulate deep inside the body, and treating amyloidosis.
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Base de dados:
MEDLINE
Assunto principal:
Oxigênio
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article