Helmholtz Gemeinschaft


Small molecules targeting human N-acetylmannosamine kinase

Item Type:Article
Title:Small molecules targeting human N-acetylmannosamine kinase
Creators Name:Hinderlich, S. and Neuenschwander, M. and Wratil, P.R. and Oder, A. and Lisurek, M. and Nguyen, L.D. and von Kries, J.P. and Hackenberger, C.P.R.
Abstract:N-acetylmannosamine kinase (MNK) plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. In search of effective inhibitors of MNK we applied high-throughput screening of drug-like small molecules. By applying different orthogonal assays for their validation we identified four potential MNK-specific inhibitors with IC(50) values in the low-micromolar range. Molecular modelling of the inhibitors into the active site of MNK supports their binding to the sugar or the ATP-binding pocket of the enzyme or both. These compounds are promising for downregulation of the sialic acid content of glycoconjugates and for studying the functional contribution of sialic acids to disease development.
Keywords:High-Throughput Screening, Inhibitors, N-Acetylmannosamine Kinases, Sialic Acids, Small Molecules
Page Range:1279-1285
Date:4 July 2017
Official Publication:https://doi.org/10.1002/cbic.201700066
PubMed:View item in PubMed

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