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Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions
Published on: November 12, 2017
Daño en el ADN por fasicularina
Sanjay Dutta1, Hideki Abe, Sakae Aoyagi
1School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Journal of the American Chemical Society
|October 27, 2005
Resumen
La fasicularina, un nuevo alcaloide de chorros de mar, daña el ADN al alquilar los residuos de guanina. Este compuesto natural forma un ion aziridinium, similar a ciertos fármacos de quimioterapia, ofreciendo nuevos conocimientos sobre los productos naturales que dañan el ADN.
Área de la Ciencia:
- Química de Productos Naturales Química de Productos Naturales
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- Fasicularin es un nuevo alcaloide que contiene tiocianato aislado de la ascidiana * Nephteis fasicularis *.
- Estudios anteriores sugirieron que la fasicularina exhibe propiedades citotóxicas potencialmente a través del daño del ADN.
Objetivo del estudio:
- Para dilucidar el mecanismo por el cual la fasicularina induce daño al ADN.
- Para caracterizar las especies químicas involucradas en la escisión del ADN mediada por fasicularina.
Principales métodos:
- Análisis de secuencia en gel de un duplex de ADN marcado con 5'-32P tratado con fasicularina.
- Análisis bioquímicos para identificar lesiones en el ADN y reactivos intermedios.
Principales resultados:
- El tratamiento con fasicularina causó la escisión selectiva de las hebras en los residuos de guanina en el ADN.
- El mecanismo de daño del ADN implica la alquilación de la guanina por un ion aziridinium derivado de la fasicularina.
- Esta formación de iones de aziridinio es análoga a la de los agentes alquiladores anticancerígenos utilizados clínicamente.
Conclusiones:
- La fasicularina es el primer producto natural identificado para generar un ion de aziridinio que alquila el ADN.
- El mecanismo de acción de la fasicularina proporciona un nuevo modelo de producto natural para la alquilación del ADN relevante para el desarrollo de fármacos contra el cáncer.
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