Cancer fighting molecules discovered

An enzyme-blocker with a new mechanism of action has been discovered by scientists at the University of East Anglia, and has the potential to fight cancer and other diseases.

Researchers from the school of pharmacy studied inhibitor candidates for glycosyltransferases (GalTs), enzymes which are used by biological cells to convert simple sugars into chains and branched structures. GalTs are used in the synthesis of cell surface sugars or glycans which are involved in cellular communication.
“These complex glycans are involved in many of the contacts biological cells make with other cells, e.g. during cancer metastasis, bacterial infections and inflammatory processes,” lead author Dr Gerd Wagner told Laboratory News.

Wagner said GalTs are involved in pathological processes like cancer metastasis and inflammation, so inhibiting them is a promising strategy to interfere with these processes.

Researchers based their inhibitors on UDP-Galactose, the natural donor substrate for GalTs. Together with colleagues at the Carlsberg Research Centre in Denmark, they focused on the modification of the uracil base on UDP-Galactose.

“This modification is at the heart of the new mechanism of action: in order to function properly, many GalTs have to change their shape during the sugar transfer reaction,” Wagner told Laboratory News, “Our inhibitor blocks this conformational change and locks the GalT in a shape in which it is not catalytically active. This is a completely new way of inhibiting these enzymes.”

Wagner believes that – while the inhibitor has not been shown to be effective in cellular experiments – the discovery may lead to new therapeutic drugs to treat cancer, inflammation and infection. He said the results provide a general strategy for how to design and improve inhibitors in the future and can provide valuable guidance for the development of new anti-cancer and anti-infective drug candidates.