Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix Academic Article uri icon


MeSH Major

  • Alkenes
  • Apoptosis
  • Bridged-Ring Compounds
  • Leukemia, Experimental
  • Molecular Mimicry
  • Peptide Fragments
  • Peptides
  • Proto-Oncogene Proteins


  • BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways.

publication date

  • September 3, 2004



  • Academic Article



  • eng

PubMed Central ID

  • PMC1360987

Digital Object Identifier (DOI)

  • 10.1126/science.1099191

PubMed ID

  • 15353804

Additional Document Info

start page

  • 1466

end page

  • 70


  • 305


  • 5689