The innovative technique of hydrocarbon stapling in peptides is introducing valuable new functionality to peptide-related research. AnaSpec is pleased to offer custom synthesis of hydrocarbon-stapled peptides.

Hydrocarbon-stapled peptides are peptides capable of forming stable alpha helical structure as a result of “hydrocarbon stapling.”^1,2 Many biological pathways, such as signal transduction, occur because of intracellular protein-protein interactions, which frequently are mediated by the α-helix structures of proteins. However, the use of short protein fragments (peptides) leads to a loss of secondary structure, which makes them susceptible to proteolysis and impermeable across cell membrane.¹ Verdine’s group has shown that these problems could be overcome by a chemical modification of an alpha-helical peptide they termed hydrocarbon-stapled peptide.^1,2 The modified hydrocarbon-stapled peptide is helical, relatively protease resistant, cell-permeable and binds with increased binding affinity to its target. Hydrocarbon stapling may provide a useful strategy in researching experimental and therapeutic modulation of protein-protein interactions as well as in in vivo pharmacokinetics studies.

Figure 1. Strategy for hydrocarbon-stapled peptide with enhanced α-helical structure.

In addition to offering stapled peptides [(i and i+4) and (i and i+7)] custom synthesis service, AnaSpec is very pleased to offer Fmoc amino acids for use in synthesizing stapled peptides (Table 1); as well as three GO™ (catalog) stapled peptides (Table 2).

To view a paper from the Journal of Molecular Biology entitled “A Cell-penetrating Helical Peptide as a Potential HIV-1 Inhibitor,” reported by scientists from the Lindsley F. Kimball Research Institute of the New York Blood Center, New York Structural Biology, AnaSpec, Inc. and the National Cancer Institute-Frederick, please click here.

AnaSpec presented a poster on hydrocarbon-stapled peptides at the 20^th American Peptide Society. Click here to download the PDF

Table 1. Fmoc amino acids for the synthesis of stapled peptides.

Table 2. Listing of GO™ (catalog) stapled peptides.

References:
1. Walensky, LD. et al. Science 305, 1466 (2004).
2. Schafmeister, CE. et al. J. Am. Chem. Soc. 122, 5891 (2000).
3. Zhang, HT. et al. J. Mol. Biol. 378(3), 565-580 (2008).