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

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 ?M range among all the substrates tested and successfully reduced cell surface sialylation in Jurkat cells.

SUBMITTER: Nieto-Garcia O

PROVIDER: S-EPMC6013775 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Nieto-Garcia Olaia O Wratil Paul R PR Nguyen Long D LD Böhrsch Verena V Hinderlich Stephan S Reutter Werner W Hackenberger Christian P R CPR

Chemical science 20160219 6

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 t ...[more]

PMID: 30155038

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