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Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14677-14681. doi: 10.1002/anie.201708237. Epub 2017 Oct 10.

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

Author information

1
Institute of Pathology, Department of Applied Tumor Biology, Faculty of Medicine, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
2
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, 19104-6323, USA.
3
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinaerstr. 13, 80539, Munich, Germany.
4
Centro de Investigaciones Biológicas, CSIC Ramiro de Maeztu, 9, 28040, Madrid, Spain.
5
Institute for Computational Molecular Science, Temple University, Philadelphia, Pennsylvania, 19122, USA.

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.

KEYWORDS:

agglutination; gangliosides; glycosylation; self-assembly; tumors

PMID:
28940633
DOI:
10.1002/anie.201708237
[Indexed for MEDLINE]

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