Scientists have found a way to create artificial sugars that could lead to better ways to diagnose and treat diseases more accurately.

"Our findings have the potential to drive significant future translational applications in human health and disease." Dr Yan Liu Department of Metabolism, Digestion and Reproduction

The new collaborative research, from academic and industry experts in Europe, including Imperial College London, shows a way to create unnatural sugars that could block pathogens. 

The findings, published in Nature Communications, offer a promising avenue to new drugs and could also open doors in diagnostics by ‘capturing’ the pathogens or their toxins.

The crucial role of sugars

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 be bound by many different proteins, making it hard to understand exactly what’s happening in the body. This has made it difficult to develop precise medical tests and treatments.

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. 

They found that some of the fluorine-containing sugars they prepared could be used to detect specifically 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.

Artificial “fluoro-sugars”

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. Artificial “fluoro-sugars” also offer an alternative to antibodies in low-cost diagnostics, which do not require animal tests to discover, and are heat stable.

Speaking about Imperial's role in the research, Dr Yan Liu, head of Imperial’s Carbohydrate Microarray Facility, said "In this consortium project, our group led the interaction screening analyses using our state-of-the-art glycan microarray system. Our platform revealed distinctive ‘interaction codes’ for various glycan-binding proteins targeting the same natural glycan structure, thanks to our unique set of synthetic, fluorinated glycans.

"This approach uncovers new insights into glycan recognition, offering a level of precision that is not possible with natural glycans. Our findings have the potential to drive significant future translational applications in human health and disease."

This collaborative research was supported by BBSRC programme ‘Chemo-enzymatic Production of Specialty Glycans’, and included researchers from eight universities, including Imperial College London, Manchester, Leeds, Warwick, Southampton, York, Bristol, and Ghent University in Belgium and the biotechnology company Prozomix.

Figure prepared by Kristian Hollie and Bruce Turnbull (University of Leeds) and Antonio di Maio (Imperial College London).

Content for this news story was adapted from a University of Manchester press release.

Synthesis and screening of a library of Lewis x deoxyfluoro-analogues reveals differential recognition by glycan-binding partners. Hollingsworth, K., Di Maio, A., Richards, SJ. et al. Nature Communications.15, 7925 (2024). https://doi.org/10.1038/s41467-024-51081-7