Synthetic glycopeptides reveal the glycan specificity of HIV-neutralizing antibodies

Nat Chem Biol. 2013 Aug;9(8):521-6. doi: 10.1038/nchembio.1288. Epub 2013 Jun 30.


A new class of glycan-reactive HIV-neutralizing antibodies, including PG9 and PG16, has been recently discovered that seem to recognize previously uncharacterized glycopeptide epitopes on HIV-1 gp120. However, further characterization and reconstitution of the precise neutralizing epitopes are complicated by the heterogeneity of glycosylation. We report here the design, synthesis and antigenic evaluation of new cyclic V1V2 glycopeptides carrying defined N-linked glycans at the conserved glycosylation sites (Asn160 and Asn156 or Asn173) derived from gp120 of two HIV-1 isolates. Antibody binding studies confirmed the necessity of a Man₅GlcNAc₂ glycan at Asn160 for recognition by PG9 and PG16 and further revealed a critical role of a sialylated N-glycan at the secondary site (Asn156 or Asn173) in the context of glycopeptides for antibody binding. In addition to defining the glycan specificities of PG9 and PG16, the identified synthetic glycopeptides provide a valuable template for HIV-1 vaccine design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • AIDS Vaccines / chemistry
  • AIDS Vaccines / immunology
  • Antibodies, Neutralizing / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Glycopeptides / chemical synthesis*
  • Glycopeptides / chemistry
  • Glycopeptides / immunology*
  • HIV-1 / immunology*
  • Polysaccharides / chemistry*
  • Polysaccharides / immunology*


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Epitopes
  • Glycopeptides
  • Polysaccharides

Associated data

  • PubChem-Substance/163565242
  • PubChem-Substance/163565243
  • PubChem-Substance/163565244