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「私たちは変われる」グレタさん COP25で行動を訴える

地球温暖化対策を話し合う国連の会議、「COP25」の会場を訪れているスウェーデンの16歳、グレタ・トゥーンベリさんは、スペインの閣僚らとともに公式イベントに登場...

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Stereodivergent synthesis of right- and left-handed iminoxylitol heterodimers and monomers. Study of their impact on β-glucocerebrosidase activity.

著者 Stauffert F , Serra-Vinardell J , Gómez-Grau M , Michelakakis H , Mavridou I , Grinberg D , Vilageliu L , Casas J , Bodlenner A , Delgado A , Compain P
Org Biomol Chem.2017 Apr 12 ; ():.
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A library of dimers and heterodimers of both enantiomers of 2-O-alkylated iminoxylitol derivatives has been synthesised and evaluated on β-glucocerebrosidase (GCase), the enzyme responsible for Gaucher disease (GD). Although the objective was to target simultaneously the active site and a secondary binding site of the glucosidase, the (-)-2-iminoxylitol moiety seemed detrimental for imiglucerase inhibition and no significant enhancement was obtained in G202R, N370S and L444P fibroblasts. However, all compounds having at least one (+)-2-O-alkyl iminoxylitol are GCase inhibitors in the nano molar range and are significant GCase activity enhancers in G202R fibroblats, as confirmed by a decrease of glucosylceramide levels and by co-localization studies.
PMID: 28401966 [PubMed - as supplied by publisher]
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