Reaction of a programmable glycan presentation of glycodendrimersomes and cells with engineered human lectins to show the sugar functionality of the cell surface
| Autor: | Michael L. Klein, Sabine Vértesy, Samuel E. Sherman, Virgil Percec, Qi Xiao, Cody Dazen, Xuhao Zhou, Jürgen Kopitz, Malwina Michalak, Anna-Kristin Ludwig, Antonio A. Romero, Hans-Joachim Gabius, Herbert Kaltner |
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| Přispěvatelé: | National Science Foundation (US) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycan Agglutination Glycosylation Cell 01 natural sciences Catalysis 03 medical and health sciences chemistry.chemical_compound Polysaccharides Lectins Gangliosides medicine Humans Tumors Ganglioside biology 010405 organic chemistry Chemistry Cell Membrane Lectin General Medicine General Chemistry Adhesion Self-assembly Ligand (biochemistry) 0104 chemical sciences 030104 developmental biology medicine.anatomical_structure Biochemistry biology.protein Biophysics Sugars Linker |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 10 p.-6 fig.-22 p. inf. supl. Kopitz, Jürgen et al. 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. Financial support from the National Science Foundation (grants DMR-1066116 and DMR-1120901), the P. Roy Vagelos Chair at the University of Pennsylvania (all to V.P.), and the National Science Foundation (grant DMR-1120901 to M.L.K.) are gratefully acknowledged |
| Databáze: | OpenAIRE |
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