ArticleThe Journal of biological chemistry2012
Metabolic inhibition of sialyl-Lewis X biosynthesis by 5-thiofucose remodels the cell surface and impairs selectin-mediated cell adhesion.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
- L-Fucose: a dietary sugar with multifaceted potential in the biology and therapy of cancer.Nature reviews. Cancer · 2026Review
- Chemical Strategies to Custom-Modify α(1→3)-Fucosylated Glycan Motifs of the Human Glycocalyx.JACS Au · 2025Review
- Realizing the promise of 'La Dolce Vita' via chemical biology: glycan-motif editing of sLeThe FEBS journal · 2025Review
- A gram-scale synthesis of β-L-carbafucose for engineering antibody glycans.Communications chemistry · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- NIR-II scattering gold superclusters for intravascular optical coherence tomography molecular imaging.Nature nanotechnology · 2025Article
- 2,2-Difluoro Derivatives of Fucose Can Inhibit Cell Surface Fucosylation without Causing Slow Transfer to Acceptors.JACS Au · 2024Article
- A novel dual-recognition fluorescent biosensor for sialyl-LewisMikrochimica acta · 2024Article
- A metabolic inhibitor blocks cellular fucosylation and enables production of afucosylated antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Rapid Protocol for Preparing 8-Aminopyrene-1,3,6-Trisulfonate-Labeled Glycans for Capillary Electrophoresis-Based Enzyme Assays.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions.Frontiers in immunology · 2023Review
- New Opportunities in Glycan Engineering for Therapeutic Proteins.Antibodies (Basel, Switzerland) · 2022Review
- Fluorinated rhamnosides inhibit cellular fucosylation.Nature communications · 2021Article
- Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors.Antibodies (Basel, Switzerland) · 2021Review
- Use of 5-Thio-L-Fucose to modulate binding affinity of therapeutic proteins.Biotechnology and bioengineering · 2021Article
- Synthetic Fluorinated l-Fucose Analogs Inhibit Proliferation of Cancer Cells and Primary Endothelial Cells.ACS chemical biology · 2020Article
- Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.International journal of molecular sciences · 2020Article
- Robustness in glycosylation systems: effect of modified monosaccharides, acceptor decoys and azido sugars on cellular nucleotide-sugar levels and pattern of N-linked glycosylation.Molecular omics · 2020Article
- Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review.Molecules (Basel, Switzerland) · 2020Review
- A Polyamidoamine Dendrimer-Based Electrochemical Immunosensor for Label-Free Determination of Epithelial Cell Adhesion Molecule- Expressing Cancer Cells.Sensors (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sialyl-Lewis X (sLe(X)) is a tetrasaccharide that serves as a ligand for the set of cell adhesion proteins known as selectins. This interaction enables adhesion of leukocytes and cancer cells to endothelial cells within capillaries, resulting in their extravasation into tissues. The last step in sLe(X) biosynthesis is the α1,3-fucosyltrasferase (FUT)-catalyzed transfer of an L-fucose residue to carbohydrate acceptors. Impairing FUT activity compromises leukocyte homing to sites of inflammation and renders cancer cells less malignant. Inhibition of FUTs is, consequently, of great interest, but efforts to generate glycosyltransferase inhibitors, including FUT inhibitors, has proven challenging. Here we describe a metabolic engineering strategy to inhibit the biosynthesis of sLe(X) in cancer cells using peracetylated 5-thio-L-fucose (5T-Fuc). We show that 5T-Fuc is taken up by cancer cells and then converted into a sugar nucleotide analog, GDP-5T-Fuc, that blocks FUT activity and limits sLe(X) presentation on HepG2 cells with an EC(50) in the low micromolar range. GDP-5T-Fuc itself does not get transferred by either FUT3 or FUT7 at a measurable rate. We further demonstrate that treatment of cells with 5T-Fuc impaired their adhesive properties to immobilized adhesion molecules and human endothelial cells. 5T-Fuc, therefore, is a useful probe that can be used to modulate sLe(X) levels in cells to evaluate the consequences of inhibiting FUT-mediated sLe(X) formation. These data also reveal the utility of using sugar analogues that lead to formation of donor substrate analogues within cells as a general approach to blocking glycosyltransferases in cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.