title: Virus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection.
abstract: Ligand polyvalency is a powerful modulator of protein-receptor interactions. Host-pathogen infection interactions are often mediated by glycan ligand-protein interactions, yet its interrogation with very high copy number ligands has been limited to heterogenous systems. Here we report that through the use of nested layers of multivalency we are able to assemble the most highly valent glycodendrimeric constructs yet seen (bearing up to 1,620 glycans). These constructs are pure and well-defined single entities that at diameters of up to 32 nm are capable of mimicking pathogens both in size and in their highly glycosylated surfaces. Through this mimicry these glyco-dendri-protein-nano-particles are capable of blocking (at picomolar concentrations) a model of the infection of T-lymphocytes and human dendritic cells by Ebola virus. The high associated polyvalency effects (β>10(6), β/N ~10(2)-10(3)) displayed on an unprecedented surface area by precise clusters suggest a general strategy for modulation of such interactions.
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Renato
authors.initials: R
authors.lastname: Ribeiro-Viana
authors.forename: Macarena
authors.initials: M
authors.lastname: Sánchez-Navarro
authors.forename: Joanna
authors.initials: J
authors.lastname: Luczkowiak
authors.forename: Julia R
authors.initials: JR
authors.lastname: Koeppe
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado
authors.forename: Javier
authors.initials: J
authors.lastname: Rojo
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Davis
mesh_terms: D015815:Cell Adhesion Molecules / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000821:virology; D029043:Ebolavirus; D006023:Glycoproteins / Q000737:chemistry / Q000627:therapeutic use*; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000821:virology; D037181:Lectins, C-Type / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000821:virology; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin