Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules.
J Am Chem Soc
; 146(14): 9779-9789, 2024 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-38561350
ABSTRACT
Protein O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of the homeostasis of O-GlcNAcylation has been linked to various human diseases, including cancer, diabetes, and neurodegeneration. However, there are limited chemical tools for protein- and site-specific O-GlcNAc modification, rendering the precise study of the O-GlcNAcylation challenging. To address this, we have developed heterobifunctional small molecules, named O-GlcNAcylation TArgeting Chimeras (OGTACs), which enable protein-specific O-GlcNAcylation in living cells. OGTACs promote O-GlcNAcylation of proteins such as BRD4, CK2α, and EZH2 in cellulo by recruiting FKBP12F36V-fused O-GlcNAc transferase (OGT), with temporal, magnitude, and reversible control. Overall, the OGTACs represent a promising approach for inducing protein-specific O-GlcNAcylation, thus enabling functional dissection and offering new directions for O-GlcNAc-targeting therapeutic development.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
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Journal of the american chemical society
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J. am. chem. soc
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Hong Kong