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PDBsum entry 6hmh
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References listed in PDB file
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Key reference
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Title
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From 1,4-Disaccharide to 1,3-Glycosyl carbasugar: synthesis of a bespoke inhibitor of family gh99 endo-α-Mannosidase.
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Authors
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D.Lu,
S.Zhu,
L.F.Sobala,
G.Bernardo-Seisdedos,
O.Millet,
Y.Zhang,
J.Jiménez-Barbero,
G.J.Davies,
M.Sollogoub.
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Ref.
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Org Lett, 2018,
20,
7488-7492.
[DOI no: ]
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PubMed id
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Abstract
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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.
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