Design and synthesis of a template-assembled oligomannose cluster as an epitope mimic for human HIV-neutralizing antibody 2G12

Abstract

The synthesis and antibody-binding affinity of a novel template-assembled oligomannose cluster as an epitope mimic for human anti-HIV antibody 2G12 are described. Cholic acid was chosen as the scaffold and three high-mannose type oligosaccharide (Man₉GlcNAc₂Asn) moieties were selectively attached at the 3α, 7α, and 12α-positions of the scaffold through a series of regioselective transformations. Binding studies revealed that the synthetic oligosaccharide cluster is 46-fold more effective than the subunit Man₉GlcNAc₂Asn in inhibiting 2G12-binding to immobilized gp120. The scaffold approach described in this paper provides an avenue to designing more effective epitope mimics for antibody 2G12 in the hope of developing a carbohydrate-based vaccine against HIV-1.