NMR and molecular recognition of compounds related to the immune system

  1. NOBRE COELHO, HELENA MARIA
Dirigida por:
  1. Filipa Margarida Barradas de Morais Marcelo Director/a
  2. Jesús Jiménez Barbero Director/a

Universidad de defensa: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Fecha de defensa: 25 de marzo de 2019

Tribunal:
  1. María Nuria Sotomayor Anduiza Presidente/a
  2. Alma Rosa López Álvarez Secretario/a
  3. Francisco Javier Cañada Vicinay Vocal
  4. Eurico Cabrita Vocal
  5. Francisco Corzana López Vocal
Departamento:
  1. Química Orgánica e Inorgánica

Tipo: Tesis

Teseo: 149457 DIALNET lock_openADDI editor

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.