Reaction of a Programmable Glycan Presentation of Glycodendrimersomes and Cells with Engineered Human Lectins To Show the Sugar Functionality of the Cell Surface

• Published in: Angewandte Chemie International Edition Vol. 56; no. 46; pp. 14677 - 14681
• Main Authors: Kopitz, Jürgen, Xiao, Qi, Ludwig, Anna‐Kristin, Romero, Antonio, Michalak, Malwina, Sherman, Samuel E., Zhou, Xuhao, Dazen, Cody, Vértesy, Sabine, Kaltner, Herbert, Klein, Michael L., Gabius, Hans‐Joachim, Percec, Virgil
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 13.11.2017
• Edition: International ed. in English
• Subjects: agglutination; Cell surface; Diagnostic systems; Galectin-1; gangliosides; Glycan; glycosylation; Lectins; Oligomers; self-assembly; Sugar; tumors; agglutination; gangliosides; self-assembly; glycosylation; tumors
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201708237

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. Carbohydrate‐directed cell adhesion: Chemical programming of the glycan presentation of glycodendrimersomes (GDSs) and the responsiveness of cells to lectin binding have been combined to define the structure–activity relationships for trans‐bridging and cis‐crosslinking of human lectins. Consequences of structural engineering of both lectin and glycan topology are explored and quantified (Gal‐1=galectin‐1).