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Kopitz J , Xiao Q , Ludwig AK , Romero A , Michalak M , Sherman SE , Zhou X , Dazen C , Vertesy S , Kaltner H , Klein ML , Gabius HJ , Percec V
Reaction of a Programmable Glycan Presentation of Glycodendrimersomes and Cells with Engineered Human Lectins To Show the Sugar Functionality of the Cell Surface
Angew Chem Int Ed Engl. 2017 Nov 13;56(46) :14677-14681
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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.
1521-3773 Kopitz, Jurgen ORCID: http://orcid.org/0000-0003-3640-8182 Xiao, Qi ORCID: http://orcid.org/0000-0002-6470-0407 Ludwig, Anna-Kristin Romero, Antonio Michalak, Malwina Sherman, Samuel E ORCID: http://orcid.org/0000-0001-7826-7088 Zhou, Xuhao Dazen, Cody Vertesy, Sabine Kaltner, Herbert Klein, Michael L Gabius, Hans-Joachim ORCID: http://orcid.org/0000-0003-3467-3900 Percec, Virgil ORCID: http://orcid.org/0000-0001-5926-0489 Journal Article Germany Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14677-14681. doi: 10.1002/anie.201708237. Epub 2017 Oct 10.