In a groundbreaking discovery at the University of Dundee, a new class of molecular glue has been identified that has the potential to revolutionize drug development for cancers and neurodegenerative diseases. Led by Professor Alessio Ciulli, the research team at the Centre for Targeted Protein Degradation (CeTPD) has made significant strides in understanding how these molecular glues can bind proteins crucial to the functioning of our cells, paving the way for new and innovative treatment strategies.

The newly identified class of “intramolecular bivalent glue” acts as a bridge between proteins that would otherwise remain separate, allowing them to interact in a way that could be exploited for therapeutic purposes. This discovery has major implications for the pharmaceutical industry, particularly in the development of drugs targeting cancer, neurodegenerative diseases, and other conditions driven by proteins that were previously considered difficult to target.

Targeted protein degradation (TPD) is an emerging field in drug development that focuses on utilizing the cell’s recycling systems to eliminate disease-causing proteins. By using small molecules known as degraders to recruit target proteins to enzymes called ubiquitin E3 ligases, researchers can tag these proteins for destruction, ultimately leading to the removal of the harmful molecules from the cell. The discovery of intramolecular bivalent glues represents a novel mechanism within the TPD framework, offering a new approach to destabilizing disease-causing proteins.

The research team at Dundee, in collaboration with partners at the Research Center for Molecular Medicine and other institutions, has uncovered a unique mechanism by which molecular glues bind to target proteins. By attaching to two different regions of the same protein, these intramolecular bivalent glues induce a rearrangement of the protein structure, facilitating its interaction with E3 ligases. This innovative approach provides a new path for drug development, offering the potential to transform the treatment landscape for a variety of diseases.

The discovery of intramolecular bivalent glues has opened up a new frontier in drug development, shedding light on previously unknown features of molecular glues and their potential therapeutic applications. By visualizing the precise mechanism of action of these compounds, researchers now have a deeper understanding of how to exploit molecular glues for targeted protein degradation. This knowledge has the potential to catalyze the development of new classes of drugs and transform the way we approach disease treatment.

As Professor Alessio Ciulli notes, the impact of this discovery cannot be overstated. The identification of intramolecular bivalent glues represents a significant advancement in our understanding of targeted protein degradation and opens up new possibilities for drug development. This research has the potential to drive innovation within the pharmaceutical industry and pave the way for more effective treatments for a wide range of diseases. The future of drug development looks brighter than ever, thanks to the groundbreaking work being done at the University of Dundee.

Chemistry

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