Synthesis and Evaluation of Prodrug Iminosugars

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

In order to dissect the molecular basis of cereal starch metabolism, this project will
take a novel chemical genetics approach through the employment of small
molecule inhibitors to directly manipulate carbohydrate-active enzyme activities in
germinating barley seed.

Based on recent results from Prof Field’s group, this project concerns the
development of a series of enzymatically hydrolysable alpha-1,4-glycosylated
iminosugars with tissue-specific activity in germinating barley seeds, acting as
novel pro-drug inhibitors of alpha-glucosidase and control enzymatically noncleavable
analogues. This will involve the exploration of new chemical and
enzymatic routes for the synthesis of the target molecules, in vitro enzyme
inhibition studies through activity assays against barley glycosidases, analysis of
enzyme-inhibitor complexes by X-ray crystallography, and in vivo analysis on
germinating barley seed (phenotype screening as well as metabolite and
glycoprotein N-glycan analysis).

unavailable