Fluorinated rhamnosides inhibit cellular fucosylation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34857733.
- Also identified by DOI 10.1038/s41467-021-27355-9 and PMC identifier 8640046.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Enzyme Inhibitors
- Fucose
- Guanosine Diphosphate Fucose
- Hydro-Lyases
- Prodrugs