Hydrocarbon stapling is a powerful technique for stabilizing the bioactive conformation of peptides while enhancing resistance to proteolytic degradation. Stapled peptides have emerged as promising therapeutic candidates for challenging targets including protein-protein interactions.
The hydrocarbon stapling technique involves the incorporation of two non-natural amino acids with olefin-containing side chains, followed by ring-closing metathesis to create a hydrocarbon bridge. This bridge constrains the peptide into an alpha-helical conformation, which is often the bioactive conformation for peptide-receptor interactions. The stapling also sterically hinders access by proteolytic enzymes, extending the peptide's half-life.
Stapled peptides offer several advantages as therapeutics. They have enhanced target affinity due to the pre-organized conformation. They have improved cell penetration compared to linear peptides, enabling targeting of intracellular targets. They have increased resistance to proteolysis, extending their in vivo half-life. These properties make stapled peptides attractive candidates for drug development.
Applications of stapled peptides include inhibiting protein-protein interactions that are difficult to target with small molecules, modulating intracellular signaling pathways, and developing novel antimicrobial agents. Several stapled peptides are in clinical development, demonstrating the therapeutic potential of this approach.
At PeptideHub, we offer hydrocarbon stapling services for research and development applications. Our experienced team can design and synthesize stapled peptides with optimized staple placement and composition. We provide high-quality stapled peptides with full analytical documentation, supporting your research and development programs.