Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN

Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3690-5. doi: 10.1073/pnas.0712326105. Epub 2008 Feb 29.


It is widely accepted that the heavily glycosylated glycoprotein gp120 on the surface of HIV-1 shields peptide epitopes from recognition by the immune system and may promote infection in vivo by interaction with dendritic cells and transport to tissue rich in CD4(+) T cells such as lymph nodes. A conserved cluster of oligomannose glycans on gp120 has been identified as the epitope recognized by the broadly HIV-1-neutralizing monoclonal antibody 2G12. Oligomannose glycans are also the ligands for DC-SIGN, a C-type lectin found on the surface of dendritic cells. Multivalency is fundamental for carbohydrate-protein interactions, and mimicking of the high glycan density on the virus surface has become essential for designing carbohydrate-based HIV vaccines and antiviral agents. We report an efficient synthesis of oligomannose dendrons, which display multivalent oligomannoses in high density, and characterize their interaction with 2G12 and DC-SIGN by a glycan microarray binding assay. The solution and the surface binding analysis of 2G12 to a prototype oligomannose dendron clearly demonstrated the efficacy of dendrimeric display. We further showed that these glycodendrons inhibit the binding of gp120 to 2G12 and recombinant dimeric DC-SIGN with IC(50) in the nanomolar range. A second-generation Man(9) dendron was identified as a potential immunogen for HIV vaccine development and as a potential antiviral agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism*
  • Carbohydrate Metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry
  • Dendrimers / metabolism*
  • Flow Cytometry
  • HIV-1 / metabolism*
  • Humans
  • Jurkat Cells
  • Lectins, C-Type / metabolism*
  • Mannose / chemical synthesis
  • Mannose / chemistry
  • Mannose / metabolism*
  • Polymers / chemistry
  • Polymers / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Dendrimers
  • Lectins, C-Type
  • Polymers
  • Receptors, Cell Surface
  • Mannose