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Ingeniería del pliegue cuádruple: la conformación de los nucleósidos determina tanto la topología de plegado como la
Chung-Fei Tang1, Richard H Shafer
1Department of Pharmaceutical Chemistry, School of Pharmacy and Graduate Group in Chemistry and Chemical Biology, University of California, San Francisco, California 94143-0446, USA.
Journal of the American Chemical Society
|April 28, 2006
Resumen
La topología plegable cuadruplex de ácido nucleico está controlada por la conformación de nucleósidos de guanina. Sustituir la guanosina de ARN (rG) por la desoxiguanosina de ADN (dG) puede revertir los pliegues y alterar la molecularidad.
Área de la Ciencia:
- Biología estructural Biología estructural.
- Química del ácido nucleico química de los ácidos nucleicos.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los cuádruplexos de ácido nucleico están formados por secuencias ricas en guanina.
- Los cuadruplexos se pliegan en topologías paralelas o antiparalelas.
- La comprensión de los factores que rigen el plegado cuádruple es crucial para las aplicaciones biológicas.
Objetivo del estudio:
- Para investigar el papel de la conformación de nucleósidos en la determinación de la topología plegable cuadruplex.
- Explorar cómo las sustituciones selectivas de nucleósidos influyen en la estructura cuadruplex y la molecularidad.
Principales métodos:
- Sustitución selectiva de la desoxiguanosina (dG) por la guanosina ribonucleosida (rG) en los aptameros de ADN y ARN.
- Análisis de los cambios resultantes en la topología plegable cuadruplex y la molecularidad.
Principales resultados:
- La sustitución de rG por dG revirtió el pliegue antiparalelo del aptamer de unión a la trombina (TBA).
- Esta sustitución convirtió un cuadríplex unimolecular en uno bimolecular.
- Sustituciones similares en un análogo TBA de todo el ARN cambiaron la topología de paralelo a antiparalelo y alteraron la configuración de la hebra.
Conclusiones:
- La fuerte preferencia de los ribonucleósidos de guanina por la anticonformación impulsa cambios en la topología cuadruplex.
- La conformación de los nucleósidos de guanina dicta el plegamiento cuádruple, la molecularidad y ofrece un método para el control estructural.
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