Issue 6, 2016

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

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

Supplementary files

Article information

Article type
Edge Article
Submitted
27 Oct 2015
Accepted
13 Feb 2016
First published
19 Feb 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 3928-3933

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

O. Nieto-Garcia, P. R. Wratil, L. D. Nguyen, V. Böhrsch, S. Hinderlich, W. Reutter and C. P. R. Hackenberger, Chem. Sci., 2016, 7, 3928 DOI: 10.1039/C5SC04082E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements