Congratulations to Filipe Rocha for successfully defending his master’s dissertation in Medicinal Chemistry entitled “Discovery of new molecules for the treatment of Machado-Joseph disease” (December 16th, 2024). Filipe’s work was developed under the supervision of Dr. Sérgio F. Sousa (BioSIM) and Prof. Fernanda Proença (University of Minho).
The research conducted throughout this thesis advanced the understanding of potential therapeutic strategies for Machado-Joseph disease by leveraging computational and synthetic approaches to identify selective protein degradation pathways.
This work involved the development of three-dimensional protein models for both wild-type and mutant Ataxin-3, followed by Molecular Dynamics simulations to explore their structural conformations. A critical pocket unique to the mutant protein was identified, enabling a focused virtual screening of chemical libraries. The top candidates were optimized based on molecular interactions and subsequently synthesized for biological testing. These findings offer a promising foundation for the design of novel PROTAC/AUTAC systems aimed at selectively degrading the pathogenic protein, paving the way for future therapeutic interventions.
This work underscores the interdisciplinary nature of drug discovery, showcasing the seamless integration of theoretical and experimental chemistry through the collaboration between BioSIM and the Chemistry Centre at the University of Minho.
