Mass spectrometry offers means to assess protein ‘glues’

Molecular glues that adhere proteins help enable the interactions between the proteins that underpin biological cell functions. In the case of some diseases, medical interventions through drugs can interrupt those interactions to disrupt the progress of illnesses.

 

By contrast, intervention may also be required to restore a healthy process and enable protein interaction.

 

Researchers at the universities of Birmingham and Leicester, together with the Dutch Eindhoven University of Technology, have tapped into the potential of mass spectrometry to achieve this.

 

Using the technique for analysis they have employed it as a means to assess the relative strengths of a variety of molecular glue candidates.

 

Dr. Aneika Leney, of the School of Biosciences at the University of Birmingham and her colleagues explained the approach in their paper ‘Tracking the mechanism of covalent molecular glue stabilization using native mass spectrometry’ published in Chemical Science.  

 

By focusing on the molecular glue MG1 they identified the different mechanisms enabling the glue to bind to proteins and stabilize their interaction. Mass spectroscopy also enabled them to assess the relative time taken by the different processes to work.

 

Dr. Peter Cossar, from Eindhoven’s Department of Biomedical Engineering stated:

 

“Understanding how molecular glues stick proteins together enables scientist to better design and build the next generation of molecular glue drugs. Mass spectrometry provides a tool to do so, by providing high fidelity information on how these unique molecules behave in real time.” 

 

The hope is that the research will form the basis for a framework to test a range molecular glues, with benefits for drug discovery.