Chemoenzymatic synthesis of HIV-1 gp41 glycopeptides: effects of glycosylation on the anti-HIV activity and alpha-helix bundle-forming ability of peptide C34

Chembiochem. 2005 Jun;6(6):1068-74. doi: 10.1002/cbic.200400440.

Abstract

C34 is a 34-mer peptide derived from the C-terminal ectodomain of HIV-1 envelope glycoprotein, gp41. The C34 region in native gp41 carries a conserved N-glycan at Asn637 and the sequence is directly involved in the virus-host membrane fusion, an essential step for HIV-1 infection. This paper describes the synthesis of glycoforms of C34 which carry a monosaccharide, a disaccharide, and a native oligosaccharide moiety. The synthesis of the glycopeptide which carries a native high-mannose type N-glycan was achieved by a chemoenzymatic approach by using an endoglycosidase-catalyzed oligosaccharide transfer as the key step. The effects of glycosylation on the inhibitory activity and the helix-bundle forming ability of C34 were investigated. It was found that glycosylation moderately decreases the anti-HIV activity of C34 and, in comparison with C34, glyco-C34 forms less compact six-helix bundles with the corresponding N-terminal peptide, N36. This study suggests that conserved glycosylation modulates the anti-HIV activity and conformations of the gp41 C-peptide, C34.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Asparagine / chemistry
  • Glycosylation
  • HIV Envelope Protein gp41 / biosynthesis*
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / pharmacology
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Polysaccharides / chemistry
  • Protein Structure, Secondary

Substances

  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Polysaccharides
  • peptide C34
  • Asparagine