Marrying Up Proteins using Molecular Glues

Protein interactions underpin every function of the human body. When they go awry, disease results. At present, drugs that can sever these interactions – and therefore halt disease – do exist. But that’s only half the story.

In some cases, absent or malformed protein interactions are the root of the problem and could benefit from drugs that serve as “glue” to bind relevant proteins together, restoring the correct balance of protein-protein interactions. Joint research undertaken by the Universities of Leicester and Birmingham in the UK explores this concept further. 

Aneika Leney, lecturer in biological mass spectrometry at the University of Birmingham says, “Richard Doveston, the other lead author on this work, is my husband, so [our departments] were a logical connection! The project largely stopped under lockdown because we were unable to enter the labs so could not perform any experiments, but we made the most of a difficult situation. It started with a conversation between my husband and I over a drink. We realized that a huge challenge in the ‘molecular glues’ field (his area of expertise) could be overcome using modern native mass spectrometry technology.”

Using mass spec, Leney and colleagues separated out single proteins, protein-protein complexes, and any “glues” present. By monitoring what happened when adding a mixture of potential glues to the proteins, the team was able to identify which offered the best performance from within a single mass spectrum.

What’s next? Leney believes that pharma companies can employ mass spectrometry as a screening tool to search for even more glues that can slow down disease progression or perhaps even treat disease.