Miller Group

Research Program

The group's research is focused around the synthesis of carbohydrates for chemical glycobiology, biomaterial and medicinal chemistry applications.

Broadly, we are interested in developing new syntheses towards the following target classes of molecule:

Sugar-nucleotide and glycosyl 1-phosphate chemical tools

GDP-D-Man sugar-nucleotide tools to probe the structure and function of GDP-mannose dehydrogenase (GMD); a key enzyme regulating the biosynthesis of alginate. Alginate is a component of the exopolysaccharide coating within the Gram-negative bacterium and opportunistic pathogen P. aeruginosa. Biosynthesis of alginate is the lead contributor in the formation of a bacterial biofilm, which presents itself in the lungs of cystic fibrosis patients. The biofilm acts as a protective microenvironment and augments the antibiotic resistance profile of P. aeruginosa.

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The development of inhibitors of GMD could offer a pathway to stop alginate production in mucoid PA strains. This is underpinned by development of structure-function tools to probe the enzyme mechanism, illustrated below (Org. Lett., 2019, https://doi.org/10.1021/acs.orglett.9b00967).


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Oligosaccharides

We are interested in the development of new synthetic methodologies to access the complex and ubiquitous glycosaminoglycan, heparan sulfate.
(See:
Chem. Commun., 2015, 51, 13846–13849; Chem. Sci., 2015, 6, 6158–6164; Nat. Commun, 2013, 4, 2016; Chem. Sci., 2013, 4, 3218-3222)


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We are also working on the synthesis of alginate-based targets in collaboration with Croda.

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Nucleoside analogues


Here we are developing syntheses of next generation nucleoside analogues for evaluation against viral and oncogenic targets. This work is being undertaken in collaboration with US Biotech
Riboscience LLC.

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We are extremely grateful to Keele University, UK research councils (EPSRC, BBSRC) and our industrial support (Riboscience LLC and Croda) for funding our research