From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue Organic Letters Année : 2018

From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase

Résumé

Understanding the enzyme reaction mechanism can lead to the design of enzyme inhibitors. A Claisen rearrangement was used to allow conversion of an α-1,4-disaccharide into an α-1,3-linked glycosyl carbasugar to target the endo-α-mannosidase from the GH99 glycosidase family, which, unusually, is believed to act through a 1,2-anhydrosugar “epoxide” intermediate. Using NMR and X-ray crystallography, it is shown that glucosyl carbasugar α-aziridines can act as reasonably potent endo-α-mannosidase inhibitors, likely by virtue of their shape mimicry and the interactions of the aziridine nitrogen with the conserved catalytic acid/base of the enzyme active site.

Domaines

Chimie organique
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Dates et versions

hal-02292793 , version 1 (20-09-2019)

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Dan Lu, Sha Zhu, Lukasz Sobala, Ganeko Bernardo-Seisdedos, Oscar Millet, et al.. From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase. Organic Letters, 2018, 20 (23), pp.7488-7492. ⟨10.1021/acs.orglett.8b03260⟩. ⟨hal-02292793⟩
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