Synthesis of inhibitors of DC-SIGN mediated infections

HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this work, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is described as a promising therapeutic target. The project is being developed within the European research Network CARMUSYS (http://www.carmusys.iiq.csic.es). Herein we show the synthesis of a small library of derivatives of a dimannoside mimic recently reported by our laboratory.1 The mimic was functionalized with two identical amide groups. Further, multivalent presentations of the prepared DC-SIGN ligands were obtained via click chemistry using dendrimeric scaffolds. The activities of the prepared molecules towards DC-SIGN were determined using surface plasmon resonance (SPR) technique. Multivalency showed significant improvement of the DC-SIGN inhibition in comparison with the corresponding monovalent ligands

Synthesis of inhibitors of DC-SIGN mediated infections

HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. On the poster, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is described as a promising therapeutic target. The project is being developed within the European research Network CARMUSYS (http://www.carmusys.iiq.csic.es/). Herein we show the synthesis of a small library of derivatives of a dimannoside mimic recently reported by our laboratory.1 The mimic was functionalized with two identical amide groups, and a tetravalent presentation was obtained using a dendron as the polyvalent scaffold. The prepared amides exhibit DC-SIGN inhibition in micromolar range, what was confirmed by measurements using surface plasma resonance (SPR) technique

Inhibition of DC-SIGN-mediated HIV infection by a linear trimannoside mimic in a tetravalent presentation

HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is a promising therapeutic target. Herein we show the ability of a new tetravalent dendron containing four copies of a linear trimannoside mimic to inhibit the trans HIV infection process of CD4+ T lymphocytes at low micromolar range. This compound presents a high solubility in physiological media, a neglectable cytotoxicity, and a long-lasting effect and is based on carbohydrate-mimic units. Notably, the HIV antiviral activity is independent of viral tropism (X4 or R5). The formulation of this compound as a gel could allow its use as topical microbicide