Active Chemistry Cells, Biochemistry & Physiology

Expediting glycosaminoglycan synthesis: expanding frontiers for carbohydrate chemical biology

Funder UKRI
Recipient organisation University of Manchester
Funding Not disclosed
Period Sept 2025 — Sept 2028

In plain English

AI plain-English summary

Carbohydrates that coat every cell in the body are notoriously difficult to synthesise in the lab, and this project aims to build them faster and more cleanly using a continuous flow of enzymes rather than traditional batch chemistry. These sugar-based molecules, called glycosaminoglycans, sit on cell surfaces and inside the body, where they orchestrate everything from inflammation to cell growth. But studying them has been held back by the slow, wasteful, and often irreproducible chemical methods used to make them. The researcher plans to replace those methods with flow biocatalysis—pumping enzymes and raw materials through a tube to produce sugar nucleotides, the building blocks cells use to assemble these carbohydrates, in a controlled and reproducible way. A second strand of the work explores a new prodrug strategy that links these sugar nucleotides to nucleoside analogues, potentially delivering antiviral or anticancer drugs more precisely to diseased cells. If successful, the technology could give biologists a reliable supply of complex carbohydrates for the first time, allowing them to probe how these molecules contribute to disease and opening a faster route to designing new therapies. The work is fundamental science with a clear translational horizon: better tools for carbohydrate chemistry mean better targets for drug development.

View original technical description
This UKRI Fellowship renewal will continue to support my development of new scientific expertise at Keele University which interfaces chemistry and biology. The overarching goal of the research is to establish efficient technologies to provide biologically important carbohydrates. Such biomolecules are positioned to modulate or mediate a huge variety of biological processes and as a result there is a sustained interest from the scientific community around the synthesis of carbohydrate structures. I will harness flow biocatalysis to enable controlled and reproducible production of the building blocks essential to carbohydrate biosynthesis, sugar nucleotides. Secondly, I seek to expand the frontier of glycoconjugate chemical biology through exploration of a novel prodrug approach, combining sugar nucleotide donors and nucleoside analogues. In undertaking this research, I will adopt a multidisciplinary approach consisting of a fusion between traditional organic chemistry, biocatalysis, the evolving field of synthesis automation, and the innovative field of chemoenzymatic synthesis. This combination will facilitate the development of a faster and greener approach to explore biologically relevant carbohydrates. This is a rapidly evolving worldwide field which is currently underrepresented in UK science. The important materials provided by the technology and knowledge developed during this Fellowship renewal will be used to probe underpinning carbohydrate biology connected to disease and aid in the design and development of new therapeutic strategies.

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Original classification

Fellowship

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