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.