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J Am Chem Soc ; 138(29): 9037-40, 2016 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-27410677

RESUMEN

The G-quadruplexes form highly stable nucleic acid structures, which are implicated in various biological processes in both DNA and RNA. Although DNA G-quadruplexes have been studied in great detail, biological roles of RNA G-quadruplexes have received less attention. Here, a screening of a chemical library permitted identification of a small-molecule tool that binds selectively to RNA G-quadruplex structures. The polyaromatic molecule, RGB-1, stabilizes RNA G-quadruplex, but not DNA versions or other RNA structures. RGB-1 intensified the G-quadruplex-mediated inhibition of RNA translation in mammalian cells, decreased expression of the NRAS proto-oncogene in breast cancer cells, and permitted identification of a novel sequence that forms G-quadruplex in NRAS mRNA. RGB-1 may serve as a unique tool for understanding cellular roles of RNA G-quadruplex structures.


Asunto(s)
G-Cuádruplex , Biosíntesis de Proteínas/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Evaluación Preclínica de Medicamentos , ARN Mensajero/química , ARN Mensajero/genética
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