Role of single disulfide linkages in the folding and activity of scyllatoxin-based BH3 domain mimetics

J Pept Sci. 2017 May;23(5):367-373. doi: 10.1002/psc.2999. Epub 2017 Mar 22.


Anti-apoptotic Bcl-2 proteins are implicated in pathogenic cell survival and have attracted considerable interest as therapeutic targets. We recently developed a class of synthetic peptide based on scyllatoxin (ScTx) designed to mimic the helical BH3 interaction domain of the pro-apoptotic Bcl-2 protein Bax. In this communication, the contribution of single disulfides in the folding and function of ScTx-Bax peptides was investigated. We synthesized five ScTx-Bax variants, each presenting a different combination of native disulfide linkage and evaluated their ability to directly bind Bcl-2 in vitro. It was determined that the position of the disulfide linkage had significant implications on the structure and function of ScTx-Bax peptides. This study underscores the importance of structural dynamics in BH3:Bcl-2 interactions and further validates ScTx-based ligands as potential modulators of anti-apoptotic Bcl-2 function. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Keywords: BH3 domain mimetic; anti-apoptotic Bcl-2 proteins; apoptosis; disulfide linkage; ligand binding; scyllatoxin.

MeSH terms

  • Biomimetic Materials / chemical synthesis*
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Disulfides / chemistry*
  • Drug Design
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Scorpion Venoms / chemistry
  • Scorpion Venoms / metabolism
  • bcl-2-Associated X Protein / chemistry


  • BAX protein, human
  • Disulfides
  • Proto-Oncogene Proteins c-bcl-2
  • Scorpion Venoms
  • bcl-2-Associated X Protein
  • leiurotoxin I