A Small-Molecule Probe with a Dual Function of miRNA Inhibition and Target identification.
Chemistry
; 29(3): e202202013, 2023 Jan 12.
Article
em En
| MEDLINE
| ID: mdl-36253322
ABSTRACT
By virtue of their key roles in pathologies, miRNAs represent a promising class of therapeutic targets. While high-fidelity small-molecule modulators of miRNAs can be identified via high-throughput screening using cellular reporter systems, their modes of action are elusive due to the lack of proper tools. Here, we report a small-molecule probe, 1 a, that is capable of elucidating its biological target along miRNA inhibition. Derived from norathyriol, a nature product, 1 a possessed a bioorthogonal alkyne moiety for subsequent labeling via copper-catalyzed azide-alkyne cycloaddition chemistry. We demonstrated that 1 a inhibited a panel of different miRNAs by blocking their loading onto argonaute 2 (AGO2), which is the key protein responsible for miRNA function. With the alkyne handle, we successfully identified AGO2 as an intracellular target of 1 a. Therefore, this work presents a novel small-molecule tool for suppressing and probing miRNA regulatory pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article