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

Academic Article
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Overview

related to degree

  • Astronomo, Rena, Ph.D. in Immunology, Virology and Glycobiology, Scripps Research 2003 - 2009
  • Wang, Sheng-Kai, Ph.D. in Chemistry, Scripps Research 2002 - 2008

authors

  • Wang, Sheng-Kai
  • Liang, P. H.
  • Astronomo, Rena
  • Hsu, T. L.
  • Hsieh, S. L.
  • Burton, Dennis
  • Wong, Chi-Huey

publication date

  • March 2008

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • 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.

subject areas

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

keywords

  • HIV vaccine
  • antiviral agent
  • glycodendron
  • high mannose
  • multivalency
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Identity

PubMed Central ID

  • PMC2268808

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0712326105

PubMed ID

  • 18310320
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Additional Document Info

start page

  • 3690

end page

  • 3695

volume

  • 105

issue

  • 10

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