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Kopitz, Jürgen; Xiao, Qi; Ludwig, Anna-Kristin; Romero, Antonio; Michalak, Malwina; Sherman, Samuel E.; Zhou, Xuhao; Dazen, Cody; Vertesy, Sabine; Kaltner, Herbert; Klein, Michael L.; Gabius, Hans-Joachim; Percec, Virgil (2017): Reaction of a Programmable Glycan Presentation of Glycodendrimersomes and Cells with Engineered Human Lectins To Show the Sugar Functionality of the Cell Surface. In: Angewandte Chemie-international Edition, Vol. 56, No. 46: pp. 14677-14681
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Abstract

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.