Pseudosaccharide functionalized dendrimers as potent inhibitors of DC-SIGN dependent Ebola pseudotyped viral infection
| Autor: | Joanna Luczkowiak, Lorena Martínez-Prats, Franck Fieschi, Anna Bernardi, Javier Rojo, José J. Reina, Ieva Sutkevičiūtė, Rafael Delgado, Michel Thépaut, Anna Daghetti, Macarena Sánchez-Navarro, Sara Sattin |
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| Rok vydání: | 2011 |
| Předmět: |
Dendrimers
Biomedical Engineering Carbohydrates Pharmaceutical Science Gene Expression Bioengineering Receptors Cell Surface Plasma protein binding Jurkat cells Antiviral Agents Cell Line Jurkat Cells Glycomimetic Dendrimer Humans Lectins C-Type Receptor Pharmacology biology Chemistry Organic Chemistry Lectin Hemorrhagic Fever Ebola Surface Plasmon Resonance Ebolavirus DC-SIGN Biochemistry Cell culture biology.protein Cell Adhesion Molecules Biotechnology Protein Binding |
| Zdroj: | Bioconjugate chemistry. 22(7) |
| ISSN: | 1520-4812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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