Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers Academic Article uri icon


MeSH Major

  • Antiviral Agents
  • HIV Envelope Protein gp41
  • HIV-1
  • Molecular Mimicry
  • Peptides
  • Protein Folding


  • Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining alpha- and beta-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that alpha/beta-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic alpha/beta-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived alpha-peptides. An optimized alpha/beta-peptide is far less susceptible to proteolytic degradation than is an analogous alpha-peptide. Our findings show how a two-stage design approach, in which sequence-based alpha-->beta replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.

publication date

  • September 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2736470

Digital Object Identifier (DOI)

  • 10.1073/pnas.0902663106

PubMed ID

  • 19706443

Additional Document Info

start page

  • 14751

end page

  • 6


  • 106


  • 35