Publication: Aplicación y nuevos desarrollos de la espectroscopía por RMN para el estudio de procesos de reconocimiento molecular entre carbohidratos y sus receptores
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2015-02-20
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Universidad Complutense de Madrid
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Abstract
Los carbohidratos constituyen uno de los tipos de biomoléculas más complejos y ubicuos, cuyo reconocimiento por parte de receptores proteicos pertenecientes a diversas familias (lectinas, anticuerpos, enzimas y virus) determina una variedad de respuestas relacionadas con procesos fisiológicos y patológicos. El conocimiento, a nivel atómico, de la estructura de los carbohidratos y de sus interacciones con proteínas es esencial para una completa comprensión de muchos procesos vitales, así como abrir la puerta a su modulación. Al mismo tiempo, la gran variabilidad estructural y versatilidad funcional de los glicanos impone la necesidad de desarrollar nuevas herramientas que permitan ampliar nuestro conocimiento sobre la estructura de estas moléculas y su reconocimiento por parte de receptores. En esta Tesis se ha hecho un uso exhaustivo de métodos de espectroscopía por resonancia magnética nuclear (RMN) para obtener información estructural sobre procesos de reconocimiento molecular en una serie de sistemas carbohidrato-proteína de interés biomédico. En distintos capítulos, esta Tesis aborda el estudio del reconocimiento molecular entre glicanos y los cuatro tipos principales de receptores de carbohidratos: lectinas, anticuerpos, enzimas y virus.
Carbohydrates are among the most ubiquitous and complex types of biomolecules in nature. Their interplay with a number of receptor families including lectins, antibodies, enzymes and viruses, triggers a variety of responses related to physiological and pathological events. Thus, knowledge on the forces that govern these interactions at atomic detail is essential for a thorough understanding of many vital processes and to open the possibility of their modulation. At the same time, the high structural variability and functional versatility of glycans call for developing new tools to probe carbohydrate conformation and recognition features by receptors. In this Thesis, we have made extensive use of NMR spectroscopy methods to gain structural insight into the interactions of a series of protein-carbohydrate systems of biomedical relevance. In addition, we present an innovative approach for conformational characterization of sugars and structural aspects of their recognition by receptors, based on the exploitation of paramagnetic effects arisen from lanthanide-binding carbohydrate conjugates
Carbohydrates are among the most ubiquitous and complex types of biomolecules in nature. Their interplay with a number of receptor families including lectins, antibodies, enzymes and viruses, triggers a variety of responses related to physiological and pathological events. Thus, knowledge on the forces that govern these interactions at atomic detail is essential for a thorough understanding of many vital processes and to open the possibility of their modulation. At the same time, the high structural variability and functional versatility of glycans call for developing new tools to probe carbohydrate conformation and recognition features by receptors. In this Thesis, we have made extensive use of NMR spectroscopy methods to gain structural insight into the interactions of a series of protein-carbohydrate systems of biomedical relevance. In addition, we present an innovative approach for conformational characterization of sugars and structural aspects of their recognition by receptors, based on the exploitation of paramagnetic effects arisen from lanthanide-binding carbohydrate conjugates
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Bioquímica y Biología Molecular I, leída el 24-10-2014