Biophysical techniques for the investigation of protein-ligand complexes
- Autores: Salvatorre Scaffidi
- Directores de la Tesis: Xavier Barril Alonso (dir. tes.), Carlos Galdeano Cantador (codir. tes.)
- Lectura: En la Universitat de Barcelona ( España ) en 2021
- Idioma: inglés
- Tribunal Calificador de la Tesis: Ernest Giralt Lledó (presid.), Cristina Mayor Ruiz (secret.), Víctor Buzón Redorta (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad de Barcelona
- Materias:
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- Resumen
Once a target is identified and characterized, the long pathway to develop a drug starts. In this process, biophysical methods have an important part to play and nowadays are firmly combined at several stages. In this scenario, using biophysical techniques, the main objective of this work is based on the identification and characterization of small molecules with the ability to bind several proteins.
Fbw7 is an E3 ligase with an important role in cancer. However, until now no Fbw7 small molecules ligands have been identified. In this thesis we have performed a FBDD program in order to identify fragments able to bind to this E3 ligase. These fragments could be employed as starting points to elucidate the best strategy to target Fbw7 and to build novel PROTAC molecules.
Due to the poor aqueous solubility of retinoids, evolution has tuned their binding to cellular proteins to address specialized physiological roles by modulating uptake, storage, and delivery to specific targets. In this thesis, we have disentangled the structure−function relationships of these protein class and disclose clues for engineering selective carriers.
Given the binding mode of fragments to a target of interest, optimization of the fragments can result laborious, difficult and time consuming. In this thesis, small molecules binding to Brd4(BD1), identified by the automated fragment evolution platform developed by our group, have been assayed and the platform validated.
