Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes
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,
Hans-Joachim Gabius
Affiliations
Paul V. Murphy
CÚRAM – SFI Research Centre for Medical Devices and the School of Chemistry, National University of Ireland Galway, University Road, Galway H91 TK33, Ireland; Corresponding author
Antonio Romero
Department of Structural and Chemical Biology, CIB Margarita Salas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain; Corresponding author
Qi Xiao
Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122, USA; Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA
Anna-Kristin Ludwig
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany
Srinivas Jogula
CÚRAM – SFI Research Centre for Medical Devices and the School of Chemistry, National University of Ireland Galway, University Road, Galway H91 TK33, Ireland
Nadezhda V. Shilova
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya str., 117437 Moscow, Russian Federation; National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, 4 Oparina str, 117997 Moscow, Russian Federation
Tanuja Singh
Glyco-Immunology Research Laboratory, Institute of Molecular and Cellular Biology, Chang-Gung-Medical College, Kwei-san, Tao-yuan 333, Taiwan
Adele Gabba
CÚRAM – SFI Research Centre for Medical Devices and the School of Chemistry, National University of Ireland Galway, University Road, Galway H91 TK33, Ireland
Bilal Javed
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA
Dapeng Zhang
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA
Francisco J. Medrano
Department of Structural and Chemical Biology, CIB Margarita Salas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain
Herbert Kaltner
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany
Jürgen Kopitz
Zentrum Pathologie, Institut für Angewandte Tumorbiologie, Medizinische Fakultät der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany; Corresponding author
Nicolai V. Bovin
Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya str., 117437 Moscow, Russian Federation; Corresponding author
Albert M. Wu
Glyco-Immunology Research Laboratory, Institute of Molecular and Cellular Biology, Chang-Gung-Medical College, Kwei-san, Tao-yuan 333, Taiwan; Corresponding author
Michael L. Klein
Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122, USA; Corresponding author
Virgil Percec
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA; Corresponding author
Hans-Joachim Gabius
Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, 80539 Munich, Germany; Corresponding author
Summary: 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.
