title: Pseudosaccharide functionalized dendrimers as potent inhibitors of DC-SIGN dependent Ebola pseudotyped viral infection.
abstract: The development of compounds with strong affinity for the receptor DC-SIGN is a topic of remarkable interest due to the role that this lectin plays in several pathogen infection processes and in the modulation of the immune response. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides in a multivalent manner. Therefore, multivalent carbohydrate systems are required to interact in an efficient manner with this receptor and compete with the natural ligands. We have previously demonstrated that linear pseudodi- and pseudotrisaccharides are adequate ligands for DC-SIGN. In this work, we show that multivalent presentations of these glycomimetics based on polyester dendrons and dendrimers lead to very potent inhibitors (in the nanomolar range) of cell infection by Ebola pseudotyped viral particles by blocking DC-SIGN receptor. Furthermore, SPR model experiments confirm that the described multivalent glycomimetic compounds compete in a very efficient manner with polymannosylated ligands for binding to DC-SIGN.
authors.affiliation: Laboratorio de Microbiologa Molecular, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, Spain.
authors.forename: Joanna
authors.initials: J
authors.lastname: Luczkowiak
authors.forename: Sara
authors.initials: S
authors.lastname: Sattin
authors.forename: Ieva
authors.initials: I
authors.lastname: Sutkevičiūtė
authors.forename: José Juan
authors.initials: JJ
authors.lastname: Reina
authors.forename: Macarena
authors.initials: M
authors.lastname: Sánchez-Navarro
authors.forename: Michel
authors.initials: M
authors.lastname: Thépaut
authors.forename: Lorena
authors.initials: L
authors.lastname: Martínez-Prats
authors.forename: Anna
authors.initials: A
authors.lastname: Daghetti
authors.forename: Franck
authors.initials: F
authors.lastname: Fieschi
authors.forename: Rafael
authors.initials: R
authors.lastname: Delgado
authors.forename: Anna
authors.initials: A
authors.lastname: Bernardi
authors.forename: Javier
authors.initials: J
authors.lastname: Rojo
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology*; D029043:Ebolavirus / Q000187:drug effects; D015870:Gene Expression; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy*; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000998:Antiviral Agents; D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D050091:Dendrimers; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin