Inhibition of GlcNAc-Processing Glycosidases by C-6-Azido-NAG-Thiazoline and Its Derivatives

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F14%3A00433505" target="_blank" >RIV/61388971:_____/14:00433505 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67179843:_____/14:00433505 RIV/61388963:_____/14:00433505

Výsledek na webu

<a href="http://dx.doi.org/10.3390/molecules19033471" target="_blank" >http://dx.doi.org/10.3390/molecules19033471</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules19033471" target="_blank" >10.3390/molecules19033471</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Inhibition of GlcNAc-Processing Glycosidases by C-6-Azido-NAG-Thiazoline and Its Derivatives

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

Inhibition of GlcNAc-Processing Glycosidases by C-6-Azido-NAG-Thiazoline and Its Derivatives

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

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Svazek periodika

19

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

3471-3488

Kód UT WoS článku

000335826800049

EID výsledku v databázi Scopus

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