Synthesis, conformation, and immunogenicity of monosaccharide-centered multivalent HIV-1 gp41 peptides containing the sequence of DP178

Bioorg Med Chem. 2004 Jun 15;12(12):3141-8. doi: 10.1016/j.bmc.2004.04.008.

Abstract

Several monosaccharide-centered multivalent HIV-1 gp41 peptides containing the sequence of DP178 were synthesized. Conformational studies showed that multivalent assembly enhanced the alpha-helical content of the peptide. Therefore, 2-, 3-, or 4-alpha-helix bundles of peptide DP178 could be obtained by assembling the peptide on a suitable bi-, tri-, or tetravalent template. Immunization studies indicated that while peptide DP178 alone was poorly immunogenic, the tetravalent peptide MVP-1 raised high titers of antibodies in mice that recognize not only peptide DP178 but also the native HIV-1 glycoprotein gp41, even in the absence of a carrier protein or adjuvant. The study suggests that carbohydrate-centered multivalent peptides provide not only a model for mimicking protein alpha-helix-bundle structure, but also an effective immunogen for raising high-titer antibodies against HIV-1 envelope glycoprotein gp41.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / immunology
  • Circular Dichroism
  • Enfuvirtide
  • Female
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / immunology*
  • HIV-1 / chemistry*
  • HIV-1 / immunology*
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Monosaccharides / chemical synthesis
  • Monosaccharides / chemistry*
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Peptide Fragments / immunology*
  • Protein Conformation

Substances

  • Antibodies, Viral
  • HIV Envelope Protein gp41
  • Monosaccharides
  • Peptide Fragments
  • Enfuvirtide