Artículo
Identification of a promising multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus
Autor/es | Varga, Norbert
Ribeiro Viana, Renato Berzi, Angela Ramdasi, Rasika Daghetti, Anna Vettoretti, Gerolamo Amara, Ali ClericI, Mario Rojo Marcos, Francisco Javier Fieschi, Franck Bernardi, Anna |
Fecha de publicación | 2014 |
Fecha de depósito | 2018-02-02 |
Publicado en |
|
Resumen | DC-SIGN is a C-type lectin receptor on antigen presenting cells (dendritic cells) which has an important role in some viral infection, notably by HIV and Dengue virus (DV). Multivalent presentation of carbohydrates on ... DC-SIGN is a C-type lectin receptor on antigen presenting cells (dendritic cells) which has an important role in some viral infection, notably by HIV and Dengue virus (DV). Multivalent presentation of carbohydrates on dendrimeric scaffolds has been shown to inhibit DC-SIGN binding to HIV envelope glycoprotein gp120, thus blocking viral entry. This approach has interesting potential applications for infection prophylaxis. In an effort to develop high affinity inhibitors of DC-SIGN mediated viral entry, we have synthesized a group of glycodendrimers of different valency that bear different carbohydrates or glycomimetic DC-SIGN ligands and have studied their DC-SIGN binding activity and antiviral properties both in an HIV and a Dengue infection model. Surface Plasmon Resonance (SPR) competition studies have demonstrated that the materials obtained bind efficiently to DC-SIGN with IC50s in the μm range, which depend on the nature of the ligand and on the valency of the scaffold. In particular, a hexavalent presentation of the DC-SIGN selective antagonist 4 displayed high potency, as well as improved accessibility and chemical stability relative to previously reported dendrimers. At low μm concentration the material was shown to block both DC-SIGN mediated uptake of DV by Raji cells and HIV trans-infection of T cells. |
Agencias financiadoras | European Union (UE) |
Identificador del proyecto | 213592 |
Cita | Varga, N., Ribeiro Viana, R., Berzi, A., Ramdasi, R., Daghetti, A., Vettoretti, G.,...,Bernardi, A. (2014). Identification of a promising multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus. Biomaterials, 35 (13), 4175-4184. |
Ficheros | Tamaño | Formato | Ver | Descripción |
---|---|---|---|---|
Identification of a promising ... | 1.840Mb | [PDF] | Ver/ | |