Suchergebnisse

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. ; This work is supported by NSF Grants DMR1066116 , DMR-1720530 , and DMR-1807127 (to V.P.), the P. Roy Vagelos Chair at the University of Pennsylvania (V.P.), the Sheikh Saqr Research Foundation (to M.L.K.), the Science Foundation Ireland (SFI) and the European Regional Development Fund (Grant Number 13/RC/2073 to CÚRAM, 16/IA/4419 to P.V.M.), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 713690 (Medtrain, to CÚRAM & S.J.), the Irish Research Council (PhD scholarship to A.G.), the Grant BFU2016-77835-R of the Spanish Ministry of Economy and Competitiveness (A.R.), as well as the COST Action CA18103 (InnoGly). We gratefully acknowledge inspiring discussions with Drs. B. Friday, A. Leddoz, and A.W.L. Nose, as well as the valuable recommendations by the reviewers. ; peer-reviewed

74 p.-5 fig.-3 schem.-6 fig. supl.-4 tab.supl.-3 schem. supl ; 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 30-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. ; This work is supported by NSF Grants DMR1066116, DMR-1720530, and DMR-1807127 (to V.P.), the P. Roy Vagelos Chair at the University of Pennsylvania (V.P.), the Sheikh Saqr Research Foundation (to M.L.K.), the Science Foundation Ireland (SFI) and the European Regional Development Fund (Grant Number 13/RC/ 2073 to CÚRAM, 16/IA/4419 to P.V.M.), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 713690 (Medtrain, to CÚRAM & S.J.), the Irish Research Council (PhD scholarship to A.G.), the Grant BFU2016-77835-R of the Spanish Ministry of Economy and Competitiveness (A.R.), as well as the COST Action CA18103 (InnoGly). ; Peer reviewed