University of Birmingham and University of Leicester researchers developed a new method for identifying drugs that ‘glue’ proteins together. The study, which was published in the journal Chemical Science, paves the way for drug developers to screen a large number of potential new drug compounds in order to develop new treatments for diseases such as breast cancer and Parkinson’s disease.
Protein interactions are critical for all cell functions. These interactions underpin all of the body’s functions in a healthy state, with any slight alteration resulting in disease.
A small number of drugs have been developed to disrupt these interactions, thereby halting the progression of the disease. However, in some diseases, the problem is caused by protein interactions that do not occur or do not occur correctly.
Thus, new drugs that act by ‘glueing’ these proteins together would be extremely effective, but their discovery would be difficult.
Researchers at the University of Birmingham’s School of Biosciences developed a system that uses mass spectrometry to determine the precise mass of a pair of proteins plus the ‘glue’, in order to determine which ‘glue’ is the strongest and thus most effective at treating the disease.
“A healthy body is highly dependent on the ability of the cells’ proteins to signal effectively,” lead author Dr Aneika Leney explained. Any incorrect signal can result in disease, and this could be due to the incorrect proteins adhering together – or proteins not joining up properly. We want a medication that will correct this. Our methods generate a’snapshot’ of what happens to the proteins when a potential drug is added, allowing us to quickly determine whether the ‘glue’ is working”.
The team collaborated with chemical biologists at the University of Leicester to validate the method using therapeutic compounds under investigation by co-lead author Dr Richard Doveston and his team.
Dr Doveston explains that finding molecules that act as glue is difficult because the situation is complicated by the presence of two proteins.
At the early stages of development, we frequently seek out molecules that serve as good starting points for further development, and thus they may be less than ideal as glues.
The high-throughput screening methods currently available to us are frequently ineffective in this context. The mass spectrometry method is fantastic because it allows us to extract a great deal of information from a small amount of data that can be gathered relatively easily and quickly.
Due to the high specificity of the glue compounds for the identified proteins, interactions with other proteins are uncommon, implying that the therapy is unlikely to produce any unexpected effects.”
“We hope that pharmaceutical companies will adopt our approach and use it to rapidly screen and test promising drug compounds that can bind proteins together to provide a therapeutic benefit,” Dr Leney added.
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