Advertisement

Facile Synthesis of Hydrocarbon-Stapled Peptides

  • Susan Del Valle
  • Emanuel Escher
  • William D. Lubell
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

The intracellular protein-protein interactions that govern many biological pathways are frequently mediated by α-helix structure of protein. Theoretically, helical peptides also can interfere with or stabilize protein-protein interactions, but native helical peptides have major shortcomings as experimental or therapeutic agents because of low potency, instability, and inefficient delivery to cells. Verdine's group [1, 2] has shown that these problems could be overcome by a chemical modification of α-helical peptides they termed hydrocarbon stapling. They used (S)-α-(2′-pentenyl)alanine containing olefin-bearing tethers to generate an all-hydrocarbon “staple” by ruthenium-catalyzed olefin metathesis. The (S)-α-(2-pentenyl)alanine peptides were made to flank three (substitution positions l and l + 4) or six (l and l+ 7) amino acids within the peptide, so that reactive olefinic residues would reside on the same face of α-helix. The modified hydrocarbon-stapled peptides are...

Keywords

Schiff Base Asymmetric Synthesis Olefin Metathesis Normal Amino Acid Helical Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Walensky, L.D., et al., Science 305, 1466–1470, (2004).CrossRefGoogle Scholar
  2. 2.
    Schafmeister, C.E., et al., J. Am. Chem. Soc. 122, 5891–5892, (2002).CrossRefGoogle Scholar
  3. 3.
    Qiu, W., et al., Tetrahedron 56, 2577–2582, (2000).CrossRefGoogle Scholar
  4. 4.
    Belokon, Y.N., et al., Tetrahedron: Asymmetry, 9, 4249–4252, (1998).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Susan Del Valle
    • 1
  • Emanuel Escher
    • 2
  • William D. Lubell
    • 3
  1. 1.Department of Chemistry & BiochemistryNew Mexico State UniversityLas CrucesUSA
  2. 2.Department of PharmacologyUniversity of Sherbrooke Medical SchoolSherbrookeCanada
  3. 3.Département de ChimieUniversité de MontréalMontréalCanada

Personalised recommendations