Reaction of a Programmable Glycan Presentation of Glycodendrimersomes and Cells with Engineered Human Lectins To Show the Sugar Functionality of the Cell Surface.
Jürgen KopitzQi XiaoAnna-Kristin LudwigAntonio RomeroMalwina MichalakSamuel E ShermanXuhao ZhouCody DazenSabine VértesyHerbert KaltnerMichael L KleinHans-Joachim GabiusVirgil PercecPublished in: Angewandte Chemie (International ed. in English) (2017)
Chemical and biological tools are harnessed to investigate the impact of spatial factors for functional pairing of human lectins with counterreceptors. The homodimeric adhesion/growth-regulatory galectin-1 and a set of covalently linked homo-oligomers from di- to tetramers serve as proof-of-principle test cases. Glycodendrimersomes provide a versatile and sensitive diagnostic platform to reveal thresholds for ligand density and protein concentration in aggregation assays (trans-activity), irrespective of linker length between lectin domains. Monitoring the affinity of cell binding and ensuing tumor growth inhibition reveal the linker length to be a bidirectional switch for cis-activity. The discovery that two aspects of lectin functionality (trans- versus cis-activity) respond non-uniformly to a structural change underscores the power of combining synthetic and biological tools to advance understanding of the sugar functionality of the cell surface.
Keyphrases
- cell surface
- endothelial cells
- single cell
- high throughput
- induced apoptosis
- induced pluripotent stem cells
- genome wide
- small molecule
- pluripotent stem cells
- oxidative stress
- binding protein
- transcription factor
- escherichia coli
- staphylococcus aureus
- cell proliferation
- cell cycle arrest
- mass spectrometry
- case report
- protein protein
- cell migration
- pseudomonas aeruginosa
- cell adhesion