Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed similar binding modes and identified new active site interactions.
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Improved production of the antidiabetic metabolite montbretin A in Nicotiana benthamiana: discovery, characterization, and use of Crocosmia shikimate shunt genes.
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Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, V6T 1Z4, Canada.
The plant-specialized metabolite montbretin A (MbA) is being developed as a new treatment option for type-2 diabetes, which is among the ten leading causes of premature death and disability worldwide. MbA is a complex acylated flavonoid glycoside produced in small amounts in below-ground organs of the perennial plant Montbretia (Crocosmia × crocosmiiflora). The lack of a scalable production system limits the development and potential application of MbA as a pharmaceutical or nutraceutical.
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Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
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Diabetes and obesity are affecting human health worldwide. Their occurrence is increasing with lifestyle choices, globalization of food systems, and economic development. The specialized plant metabolite montbretin A (MbA) is being developed as an antidiabetes and antiobesity treatment due to its potent and specific inhibition of the human pancreatic α-amylase.
View Article and Find Full Text PDFSynthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase.
Chem Sci
December 2019
Department of Chemistry , University of British Columbia, 2036 Main Mall , Vancouver BC , Canada V6T 1Z1 . Email:
Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed similar binding modes and identified new active site interactions.
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