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

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 intro...

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Autores principales: Nieto-Garcia, Olaia, Wratil, Paul R., Nguyen, Long D., Böhrsch, Verena, Hinderlich, Stephan, Reutter, Werner, Hackenberger, Christian P. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2016
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013775/
https://www.ncbi.nlm.nih.gov/pubmed/30155038
http://dx.doi.org/10.1039/c5sc04082e
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author Nieto-Garcia, Olaia
Wratil, Paul R.
Nguyen, Long D.
Böhrsch, Verena
Hinderlich, Stephan
Reutter, Werner
Hackenberger, Christian P. R.
author_facet Nieto-Garcia, Olaia
Wratil, Paul R.
Nguyen, Long D.
Böhrsch, Verena
Hinderlich, Stephan
Reutter, Werner
Hackenberger, Christian P. R.
author_sort Nieto-Garcia, Olaia
collection PubMed
description 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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spelling pubmed-60137752018-08-28 Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs Nieto-Garcia, Olaia Wratil, Paul R. Nguyen, Long D. Böhrsch, Verena Hinderlich, Stephan Reutter, Werner Hackenberger, Christian P. R. Chem Sci Chemistry 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. Royal Society of Chemistry 2016-06-01 2016-02-19 /pmc/articles/PMC6013775/ /pubmed/30155038 http://dx.doi.org/10.1039/c5sc04082e Text en This journal is © The Royal Society of Chemistry 2016 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Nieto-Garcia, Olaia
Wratil, Paul R.
Nguyen, Long D.
Böhrsch, Verena
Hinderlich, Stephan
Reutter, Werner
Hackenberger, Christian P. R.
Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
title Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
title_full Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
title_fullStr Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
title_full_unstemmed Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
title_short Inhibition of the key enzyme of sialic acid biosynthesis by C6-Se modified N-acetylmannosamine analogs
title_sort inhibition of the key enzyme of sialic acid biosynthesis by c6-se modified n-acetylmannosamine analogs
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013775/
https://www.ncbi.nlm.nih.gov/pubmed/30155038
http://dx.doi.org/10.1039/c5sc04082e
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