Design and synthesis of a template-assembled oligomannose cluster as an epitope mimic for human HIV-neutralizing antibody 2G12.
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 (Man(9)GlcNAc(2)Asn) moieties were selectively attached at the 3alpha, 7alpha, and 12alpha-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 Man(9)GlcNAc(2)Asn 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.
Li
Hengguang
H
Institute of Human Virology, University of Maryland Biotechnology Institute, University of Maryland, Baltimore, MD 21201, USA.
Wang
Lai-Xi
LX
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D057134:Antibodies, Neutralizing / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D000080908:Broadly Neutralizing Antibodies; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry*; D015483:HIV Antibodies / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis*
C529157:2G12 monoclonal antibody; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D000939:Epitopes; D015483:HIV Antibodies; D009844:Oligosaccharides; D008358:Mannose