Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N -acetylmannosamine analogs

Chemical Science
Olaia Nieto-GarciaChristian P R Hackenberger

Abstract

Synthetically accessible C6-analogs of N-acetylmannosamine (ManNAc) were tested as potential inhibitors of the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE/MNK), the key enzyme of sialic acid biosynthesis. Enzymatic experiments revealed that the modification introduced at the C6 saccharide position strongly influences the inhibitory potency. A C6-ManNAc diselenide dimer showed the strongest kinase inhibition in the low μM range among all the substrates tested and successfully reduced cell surface sialylation in Jurkat cells.

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Citations

Mar 27, 2019·Glycobiology·Sam J MoonsChristian Büll
Jul 21, 2016·Angewandte Chemie·Paul R WratilWerner Reutter
Mar 28, 2017·Chembiochem : a European Journal of Chemical Biology·Stephan HinderlichChristian P R Hackenberger
Jun 18, 2017·Chembiochem : a European Journal of Chemical Biology·Stephan HinderlichChristian P R Hackenberger

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Methods Mentioned

BETA
glycosylation
enzymatic assay
flow cytometry

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