Anaspec has announced the availability of a stapled helical peptides custom-synthesis service.
Unnatural amino acid (S5 and R8) substitutions flank three (substitution positions i and i + 4 using S5 and S5, for example XXXXX-S5-XXX-S5-XXXXX) or six standard amino acids (i and i + 7 using R8 and S5, for example XXXXXX-R8-XXXXXX-S5-XXXXX).
Many biological pathways, such as signal transduction, occur because of intracellular protein-protein interactions, which are frequently mediated by the a-helix structures of proteins; however, the use of short protein fragments (peptides) generally leads to the loss of secondary structure, such as alpha helical structure.
Short peptides are also easily degraded by proteolysis and have difficulty in intact cells penetration.
Verdine's group has shown that these problems can be overcome by chemically modifying an alpha-helical peptide it termed hydrocarbon-stapled peptide.
The modified hydrocarbon-stapled peptide was helical and relatively protease resistant.
The modification resulted in cell-permeable peptides that bind with increased binding affinity for its target.
They may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in signalling pathways related to apoptosis in cancer cells and in vivo pharmacokinetics and efficacy in disease models.
