Influence of the reducing-end anomeric configuration of the Man9 epitope on DC-SIGN recognition

High-mannose (Man(9)GlcNAc(2)) is the main carbohydrate unit present in viral envelope glycoproteins such as gp120 of HIV and the GP1 of Ebola virus. This oligosaccharide comprises the Man(9)epitope conjugated to two terminalN-acetylglucosamines by otherwise rarely-encountered beta-mannose glycosidic bond. Formation of this challenging linkage is the bottleneck of the few synthetic approaches described to prepare high mannose. Herein, we report the synthesis of the Man(9)epitope with both alpha and beta configurations at the reducing end, and subsequent evaluation of the impact of this configuration on binding to natural receptor of high-mannose, DC-SIGN. Using fluorescence polarization assays, we demonstrate that both anomers bind to DC-SIGN with comparable affinity. These relevant results therefore indicate that the more synthetically-accesible Man(9)alpha epitope may be deployed as ligand for DC-SIGN in bothin vitroandin vivobiological assays.