Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
27152630
DOI
10.1016/j.carres.2016.04.004
PII: S0008-6215(16)30100-8
Knihovny.cz E-resources
- Keywords
- GH38 family, Golgi α-mannosidase, Inhibition, Lysosomal α-mannosidase, α-Mannosidase inhibitor,
- MeSH
- Drosophila melanogaster enzymology genetics MeSH
- Enzyme Inhibitors chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Lysosomes enzymology MeSH
- Mannose chemistry MeSH
- Mannosidases antagonists & inhibitors genetics MeSH
- Models, Molecular MeSH
- Drosophila Proteins antagonists & inhibitors genetics MeSH
- Recombinant Proteins metabolism MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Enzyme Inhibitors MeSH
- Mannose MeSH
- Mannosidases MeSH
- Drosophila Proteins MeSH
- Recombinant Proteins MeSH
Nine new compounds having five- and modified six-member carbohydrate core derived from D-lyxose or D-mannose, and non-hydrolysable aglycones (benzylsulfonyl or aryl(alkyl)triazolyl) were synthesised to investigate their ability to inhibit the recombinant Drosophila melanogaster homologs of two human GH38 family enzymes: Golgi mannosidase II (dGMIIb) and lysosomal mannosidase (dLMII). Two compounds were weak selective dGMIIb inhibitors showing IC50 at mM level. Moreover, it was found that another GH38 enzyme, commercial jack bean α-mannosidase, was inhibited by triazole conjugates regardless of the carbohydrate core while the corresponding sulfones were inactive.
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