Publication: Combinando motivos canónicos y no canónicos del ADN: estructura, dinámica y reconocimiento molecular
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2021-06-10
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Universidad Complutense de Madrid
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Abstract
La estructura de doble hélice ha sido ampliamente estudiada en el campo de la biología estructural. Es la forma principal de ordenación del ADN, pero no la única posible. De hecho, hoy en día se conocen diversas estructuras alternativas del ADN, que se denominan globalmente como estructuras no canónicas. La relevancia de estas estructuras ha aumentado notablemente en los últimos años ante las numerosas evidencias de su implicación en procesos biológicos, especialmente en procesos de regulación de la génica. Además estas estructuras son interesantes desde el punto de vista biomédico, como posibles dianas farmacéuticas, y también en nanociencia, por sus posibles aplicaciones en la construcción de dispositivos de escala nanométrica. Entre las estructuras no canónicas, en esta tesis nos hemos centrado en el estudio del i-motif y el cuádruplex de guaninas (o G-cuádruplex). En ambos casos se trata de estructuras tetracatenarias de ADN. El i-motif está formado por la intercalación de pares C:C+, donde las citosinas se encuentran hemiprotonadas. El cuádruplex de guaninas está estabilizado por plataformas planas (tétradas) de cuatro guaninas. La técnica principal utilizada en esta tesis es la Resonancia Magnética Nuclear (RMN).Desde los años 80 se lleva utilizado esta potente tecnología para el análisis de biomoléculas, que permite su análisis estructural y dinámico, así como el estudio delas interacciones con compuestos de bajo peso molecular...
The double helix has been extensively studied in the Structural Biology field.This structure is the main arrangement adopted by DNA, but not the only one possible. Nowadays, several alternative DNA structures are known, which are globally termed as “non canonical” DNA structures. The relevance of these structures has increased notably in recent years due to numerous evidences of their involvement in biological processes, especially in gene regulation. Furthermore, non canonical structures are interesting from a biomedical point of view, as possible pharmaceutical targets, and also in Nanoscience because of their potential applications for building nanoscale devices. Among all these structures, in this thesis we focus in the study of the i-motif and the guanine quadruplex (or G-quadruplex). In both cases they are four-stranded DNA structures. The i-motif is formed by the intercalation of C:C+ base-pairs, inwhich the cytosines are hemiprotonated. The G-quadruplex is stabilized by flat platforms (tetrads) of four guanines. The main technique used in this thesis is NuclearMagnetic Resonance (NMR). Since the 1980s, this powerful technology has been used for the analysis of the structure and dynamcis of biomolecules, as well as the study of their interactions with low molecular weight compounds...
The double helix has been extensively studied in the Structural Biology field.This structure is the main arrangement adopted by DNA, but not the only one possible. Nowadays, several alternative DNA structures are known, which are globally termed as “non canonical” DNA structures. The relevance of these structures has increased notably in recent years due to numerous evidences of their involvement in biological processes, especially in gene regulation. Furthermore, non canonical structures are interesting from a biomedical point of view, as possible pharmaceutical targets, and also in Nanoscience because of their potential applications for building nanoscale devices. Among all these structures, in this thesis we focus in the study of the i-motif and the guanine quadruplex (or G-quadruplex). In both cases they are four-stranded DNA structures. The i-motif is formed by the intercalation of C:C+ base-pairs, inwhich the cytosines are hemiprotonated. The G-quadruplex is stabilized by flat platforms (tetrads) of four guanines. The main technique used in this thesis is NuclearMagnetic Resonance (NMR). Since the 1980s, this powerful technology has been used for the analysis of the structure and dynamcis of biomolecules, as well as the study of their interactions with low molecular weight compounds...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 19-01-2021