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Inhibition of GlcNAc-Processing Glycosidases by C-6-Azido-NAG-Thiazoline and Its Derivatives
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SYSNO ASEP 0433505 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Inhibition of GlcNAc-Processing Glycosidases by C-6-Azido-NAG-Thiazoline and Its Derivatives Author(s) Krejzová, Jana (MBU-M) RID
Šimon, Petr (MBU-M)
Ježová-Kalachová, Lubica (MBU-M) RID
Kulik, Natallia (UEK-B) RID
Bojarová, Pavla (MBU-M) ORCID
Marhol, Petr (MBU-M) RID
Pelantová, Helena (MBU-M) ORCID, RID
Cvačka, Josef (UOCHB-X) RID, ORCID
Ettrich, Rüdiger (UEK-B) RID, ORCID, SAI
Slámová, Kristýna (MBU-M) RID, ORCID
Křen, Vladimír (MBU-M) RID, ORCIDSource Title Molecules. - : MDPI - ISSN 1420-3049
Roč. 19, č. 3 (2014), s. 3471-3488Number of pages 18 s. Language eng - English Country CH - Switzerland Keywords NAG-thiazoline ; enzyme inhibition ; O-GlcNAcase Subject RIV CE - Biochemistry Institutional support MBU-M - RVO:61388971 ; RVO:67179843 - RVO:67179843 ; UOCHB-X - RVO:61388963 UT WOS 000335826800049 DOI https://doi.org/10.3390/molecules19033471 Annotation NAG-thiazoline is a strong competitive inhibitor of GH20 beta-N-acetylhexosaminidases and GH84 beta-N-acetylglucosaminidases. Here, we focused on the design, synthesis and inhibition potency of a series of new derivatives of NAG-thiazoline modified at the C-6 position. Dimerization of NAG-thiazoline via C-6 attached triazole linkers prepared by click chemistry was employed to make use of multivalency in the inhibition. Novel compounds were tested as potential inhibitors of beta-N-acetylhexosaminidases from Talaromyces flavus, Streptomyces plicatus (both GH20) and beta-N-acetylglucosaminidases from Bacteroides thetaiotaomicron and humans (both GH84). From the set of newly prepared NAG-thiazoline derivatives, only C-6-azido-NAG-thiazoline displayed inhibition activity towards these enzymes; C-6 triazole-substituted NAG-thiazolines lacked inhibition activity against the enzymes used. Docking of C-6-azido-NAG-thiazoline into the active site of the tested enzymes was performed. Moreover, a stability study with GlcNActhiazoline confirmed its decomposition at pH < 6 yielding 2-acetamido-2-deoxy-1-thio-alpha/beta-D-glucopyranoses, which presumably dimerize oxidatively into S-S linked dimers; decomposition products of NAG-thiazoline are void of inhibitory activity Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2015
Number of the records: 1