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

Olaia Nieto-Garcia, Paul R. Wratil, Long D. Nguyen, Verena Böhrsch, Stephan Hinderlich, Werner Reutter and Christian P. R. Hackenberger – 2016

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.

Titel
Inhibition of key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
Verfasser
Olaia Nieto-Garcia, Paul R. Wratil, Long D. Nguyen, Verena Böhrsch, Stephan Hinderlich, Werner Reutter and Christian P. R. Hackenberger
Datum
2016
Kennung
10.1039/C5SC04082E
Zitierweise
Chem. Sci., 2016, 7, 3928-3933
Art
Text
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