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October 20, 2023 10:00

Sala d’Actes IQAC

The PhD researcher Abdulateef Alqahtani, from the RUBAM group, will defend his PhD thesis on 20th October at 10:00h in the Sala d’Actes IQAC-CSIC.

Title: Design, synthesis and biological evaluation of novel molecules with the capacity of inducing the degradation of different proteins by direct signalling to the proteasome

Supervisor: Gemma Fabriàs

Thesis Committee: Carmen Escolano, Gemma Triola, Ana Belén Cuenca

Abstract:

Multiple PROTACs that degrade proteins relevant in several diseases have been developed, and the number is quickly increasing, indicating their therapeutic projection. Given some limitations of E3-based PROTACs such as the diversity and complexity of E3 ligases, alternative strategies in target protein degradation are pursued. The main objective of this thesis was to develop a novel type of chimeras with the capacity to induce protein degradation by direct signalling to the 26S proteasome by interacting with USP14, a 26S-associated deubiquitinating enzyme involved in substrate processing and allosteric regulation of 26S activity. The overall results obtained in the biological studies provide proof of concept for this 26S-directed PROTAC, which should expand the potential of target protein degradation.