Scientists develop artificial sugars to improve diagnosis and treatment accuracy of diseases

Scientists have found a way to create artificial sugars that could lead to better ways to diagnose and treat disease, with more precision than ever before.

Sugars play a crucial role in human health and disease, far beyond their role as a simple source of energy. Complex sugars called glycans line all of our cells and are essential for their proper functioning. However, these sugars are often hijacked by pathogens such as influenza, COVID-19, and cholera to infect us.

One of the main problems in treating and diagnosing diseases and infections is that the same glycan can bind to many different proteins, making it difficult to understand exactly what is happening in the body and making it difficult to develop accurate medical tests and treatments.

In a groundbreaking discovery, published in the journal Nature CommunicationsA collaboration of academic and industry experts in Europe, including the University of Manchester and the University of Leeds, has found a way to create unnatural sugars that could block pathogens.

The discovery offers a promising avenue for new drugs and could also open doors in diagnostics by “capturing” pathogens or their toxins.

Professor Matthew Gibson, a researcher at the Manchester Institute of Biotechnology at the University of Manchester, said: “During the COVID-19 pandemic, our team introduced the first lateral flow tests that used sugars instead of antibodies as the ‘recognition unit’. But the limitation is still the specificity and selectivity of these tests due to the promiscuity of natural sugars.

“We can now integrate these fluorosugars into our biosensing platforms with the aim of having cheap, rapid and thermally stable diagnostics suitable for low-resource environments.”

Professor Bruce Turnbull, lead author of the study from the School of Chemistry and the Astbury Centre for Structural Molecular Biology at the University of Leeds, said: “Glycans that are really important for our immune system and other biological processes that keep us healthy, are also exploited by viruses and toxins to enter our cells.

“Our work allows us to understand how human and pathogenic proteins interact in different ways with the same glycan. This will help us develop diagnostics and drugs that can distinguish between human and pathogenic proteins.”

The researchers used a combination of enzymes and chemical synthesis to alter the structure of 150 sugars by adding fluorine atoms. Fluorine is very small, meaning the sugars retain their same 3D shape, but the fluorines interfere with how proteins bind them.

Professor Sabine Flitsch, a researcher at the Manchester Institute of Biotechnology at the University of Manchester, said: “One of the key technologies used in this work is biocatalysis, which uses enzymes to produce the highly complex and diverse sugars required for the library. Biocatalysis greatly speeds up the synthesis effort required and is a much more environmentally friendly and sustainable method of producing the required fluorinated probes.”

They found that some of the sugars they prepared could be used to detect cholera toxin, a harmful protein produced by bacteria, meaning they could be used in simple, inexpensive tests, similar to lateral flow tests, which are widely used for pregnancy tests and during the COVID-19 pandemic.

Dr Kristian Hollie, who led the production of the fluorinated sugar library at the University of Leeds, said: “We used enzymes to rapidly assemble fluorinated sugar building blocks to make 150 different versions of a biologically important glycan. We were surprised to find how well natural enzymes work with these chemically modified sugars, making it a really effective strategy for discovering molecules that can bind selectively.”

The study demonstrates that artificial “fluorosugars” can be used to refine the recognition of pathogens or biomarkers, or even to discover new drugs. They also offer an alternative to antibodies in low-cost diagnostics, which do not require animal testing to be discovered and are thermostable.