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Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes

The small 3-O-sulfated galactose head group of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of head group derivatives for functionalization of amphiphilic dendrimers is performed. Ag...

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Main Authors: Murphy, Paul V. (Author) , Romero, Antonio (Author) , Xiao, Qi (Author) , Ludwig, Anna-Kristin (Author) , Jogula, Srinivas (Author) , Shilova, Nadezhda V. (Author) , Singh, Tanuja (Author) , Gabba, Adele (Author) , Javed, Bilal (Author) , Zhang, Dapeng (Author) , Medrano, Francisco J. (Author) , Kaltner, Herbert (Author) , Kopitz, Jürgen (Author) , Bovin, Nicolai V. (Author) , Wu, Albert M. (Author) , Klein, Michael L. (Author) , Percec, Virgil (Author) , Gabius, Hans-Joachim (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: iScience
Year: 2021, Volume: 24, Issue: 1, Pages: 1-11
ISSN:2589-0042
DOI:10.1016/j.isci.2020.101919
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.isci.2020.101919
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004220311160
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Author Notes:Paul V. Murphy, Antonio Romero, Qi Xiao, Anna-Kristin Ludwig, Srinivas Jogula, Nadezhda V. Shilova, Tanuja Singh, Adele Gabba, Bilal Javed, Dapeng Zhang, Francisco J. Medrano, Herbert Kaltner, Jürgen Kopitz, Nicolai V. Bovin, Albert M. Wu, Michael L. Klein, Virgil Percec, and Hans-Joachim Gabius

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520 |a The small 3-O-sulfated galactose head group of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of head group derivatives for functionalization of amphiphilic dendrimers is performed. Aggregation of resulting (biomimetic) vesicles, alone or in combination with lactose, demonstrates bridging by a tissue lectin (galectin-4). Physiologically, this can stabilize glycolipid-rich microdomains (rafts) and associate sulfatide-rich regions with specific glycoproteins. Further testing documents importance of heterobivalency and linker length. Structurally, sulfatide recognition by galectin-8 is shown to involve sphingosine's OH group as substitute for the 3′-hydroxyl of glucose of lactose. These discoveries underscore functionality of this small determinant on biomembranes intracellularly and on the cell surface. Moreover, they provide a role model to examine counterreceptor capacity of more complex glycans of glycosphingolipids and to start their bottom-up glycotope surface programming. 
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