NMR and molecular recognition of compounds related to the immune system

• Autores: Helena Maria Nobre Coelho
• Directores de la Tesis: Filipa Margarida Barradas de Morais Marcelo (dir. tes.), Jesús Jiménez Barbero (dir. tes.), Maria Esther Lete Exposito (tut. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2019
• Idioma: inglés
• Tribunal Calificador de la Tesis: María Nuria Sotomayor Anduiza (presid.), Alma Rosa López Álvarez (secret.), Eurico Cabrita (voc.), Francisco Corzana López (voc.), Francisco Javier Cañada Vicinay (voc.)
• Programa de doctorado: Programa de Doctorado en Química Sintética e Industrial por la Universidad del País Vasco/Euskal Herriko Unibertsitatea y la Universidad Pública de Navarra
• Materias:
  • Química
    • Química analítica
      • Espectroscopia de resonancia magnética
    • Bioquímica
      • Enzimología
      • Glúcidos
• Enlaces
  • Tesis en acceso abierto en: ADDI
• Resumen

  • Glycans are among the most varied and complex molecules in biological systems. The glycosylation process is the most complex and widespread modification of proteins and lipids, with an unsurpassed capacity to generate a wide array of different structures. Recognition of glycans by specific receptors translates the glycome into unprecedented biological signals in physiological and pathological events. In this work, we applied Nuclear Magnetic Resonance (NMR) spectroscopy to gain structural insights of different molecular recognition processes between glycans and diverse proteins with biomedical relevance. As key highlight, key aspects of the glycosylation mechanism of MUC1 by GalNAc-Transferases (GalNAc-Ts) have been unraveled, paying special attention to the site-specificity of the process. Furthermore, our targets have an important impact in disease, particularly, in cancer (mucin-1) and in bacterial infections (Toll-like receptor 4). Throughout this Thesis, state-of-the-art NMR experiments have been applied to dissect the molecular details of these biomolecular recognition processes. Thus, ligand-based and receptor-based methods have been used, in combination with a variety of additional experimental and theoretical techniques. Thus, biophysical, biochemical, molecular biology and computational methodologies have complemented the NMR data in order to attain a complete description of the interaction events.