Stapled peptides are short sequences that typically adopt an α‑helical structure and are conformationally constrained by a synthetic “staple” or brace inserted along the backbone. The staple is a covalent linkage between two amino acid side chains that generates a peptidic macrocycle; when two or more staples are introduced in series, the resulting constructs are often referred to as “stitched peptides”.

By locking the peptide into a preferred conformation, these covalent constraints reduce conformational entropy and stabilize the helix, which can translate into higher target affinity, improved cellular uptake, and enhanced resistance to proteolytic degradation.

All‑hydrocarbon staples formed via ring‑closing metathesis (RCM) are widely used to increase peptide stability and membrane permeability, making stapling a powerful approach to optimize the pharmacological properties of therapeutic peptides, especially those designed to modulate protein–protein interactions and other challenging targets.

At SB Peptide, we provide a range of services to support your research. Our expertise includes the design and synthesis of stapled peptides using advanced methodologies to ensure high-quality results.

Hydrocarbon‑stapled peptides are typically prepared by solid‑phase peptide synthesis, introducing two α‑methyl, α‑alkenyl amino acids that carry olefinic side chains of defined length at positions i and i+3, i+4, i+7 along the sequence. After chain assembly, the staple is formed by ring‑closing metathesis, followed by global deprotection and cleavage from the resin.

The design of stapled peptides relies on the site‑specific incorporation of non‑natural amino acids that enable controlled macrocyclization and stabilize the desired secondary structure.