Sugars play a crucial role in human health and disease, far beyond being just an energy source. Complex sugars called glycans coat all our cells and are essential for healthy function. However, these sugars are often hijacked by pathogens such as influenza, COVID-19, and cholera to infect us.
One big problem in treating and diagnosing diseases and infections is that the same glycan can bind to many different proteins, making it hard to understand exactly what’s happening in the body and has made it difficult to develop precise medical tests and treatments.
In a breakthrough, published in the journal Nature Communications, a collaboration of academic and industry experts in Europe have found a way to create unnatural sugars that could block the pathogens.
The researchers used a combination of enzymes and chemical synthesis to edit the structure of 150 sugars by adding fluorine atoms. Fluorine is very small meaning that the sugars keep their same 3D shape, but the fluorine’s interfere with how proteins bind them.
The finding offers a promising avenue to new drugs and could also open doors in diagnostics by ‘capturing’ the pathogens or their toxins.
Professor Galan said “One of the key technologies used in this work is biocatalysis, which uses enzymes to produce the very complex and diverse sugars needed for the library.
"However, enzymes can be very specific for their substrate so in order to screen a large panel of biocatalysts that can act upon unnatural glycans, we employed an approach that uses clickable positively charged imidazolium-based tags (ITags) that allows for fast screening of reactivity by mass spectrometry”.
The team found that some of the sugars they prepared could be used to detect the cholera toxin – a harmful protein produced by bacteria – meaning they could be used in simple, low-cost tests, similar to lateral flow tests, widely used for pregnancy testing and during the COVID-19 pandemic.
The study provides evidence that the artificial “fluoro-sugars” can be used to fine-tune pathogen or biomarker recognition or even to discover new drugs. They also offer an alternative to antibodies in low-cost diagnostics, which do not require animals test to discover and are heat stable.
The research team included researchers from eight different universities, including Manchester, Imperial College London, Leeds, Warwick, Southampton, York, Bristol, and Ghent University in Belgium and the biotechnology company Prozomix.