'Stapled' protein proposed for cancer treatment

Scientists from the universities of Glasgow, Leicester, Leeds and Tsukuba have created a proteomimetic version of a naturally occurring protein called TPX2. Writing in the journal ACS Chemical Biology, the researchers claim that their version of the protein could lead to a biological drug to treat cancer.

Proteomimetics are synthetic proteins that mimic the structure and interacting surfaces of natural proteins, allowing them to slip past the body’s defences and deliver a therapeutic effect for patients. Although the researchers’ proteomimetic TPX2 has the same interacting surfaces as the natural protein, it has been designed to have a higher affinity within the body.

Through a process known as ‘stapling’, the TPX2 has been altered to make it more resilient and likely to ‘stick’ to and interact with another protein called Aurora-A. Targeting Aurora-A has been proposed as a potentially useful strategy for cancer treatment.

“If you think of the naturally occurring protein as a basic model of a car, the proteomimetic version we’ve created is like a kit car version of the same vehicle but is more robust and faster,” said lead author Dr Andrew Jamieson from the University of Glasgow.

“Stapling the TPX2 protein may make it more rigid and less easily broken down by the body, so it has a greater chance to disrupt naturally occurring protein-to-protein interactions and provide longer-lasting benefit to patients.”

Dr Jamieson said the scientists are keen to take their research further and explore in more detail how their protein can be used effectively in the future.

“It’s one step closer to using custom-designed proteins as biological drugs, which could deliver a huge range of medical benefits in coming decades.”