Fluorinated rhamnosides inhibit cellular fucosylation.
Animals
Carbohydrate Sequence
Cell Line, Tumor
Cell Membrane
/ drug effects
Drug Design
Enzyme Inhibitors
/ chemical synthesis
Fucose
/ chemistry
Gene Expression
Glycosylation
/ drug effects
Guanosine Diphosphate Fucose
/ antagonists & inhibitors
Halogenation
Humans
Hydro-Lyases
/ antagonists & inhibitors
Jurkat Cells
Lymphocytes
/ cytology
Mice
Prodrugs
/ chemical synthesis
Structure-Activity Relationship
THP-1 Cells
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
12
10
2020
accepted:
12
11
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
5
1
2022
Statut:
epublish
Résumé
The sugar fucose is expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis via competitive GMDS inhibition. We demonstrate that cell permeable fluorinated rhamnose 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.
Identifiants
pubmed: 34857733
doi: 10.1038/s41467-021-27355-9
pii: 10.1038/s41467-021-27355-9
pmc: PMC8640046
doi:
Substances chimiques
Enzyme Inhibitors
0
Prodrugs
0
Guanosine Diphosphate Fucose
15839-70-0
Fucose
28RYY2IV3F
Hydro-Lyases
EC 4.2.1.-
GDPmannose 4,6-dehydratase
EC 4.2.1.47
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7024Informations de copyright
© 2021. The Author(s).
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