α-helical peptides engineered for stability, target binding, and intracellular activity.
Stapled peptides are conformationally constrained peptides designed to stabilize α-helical structure by covalently linking two side chains. By reducing flexibility, stapling can increase helical content, improve protease resistance, and strengthen target binding—especially for interfaces where helix geometry drives activity (common in protein–protein interactions)..
Bio-Synthesis manufactures stapled peptides using practical stapling routes—most commonly hydrocarbon stapling via ring-closing metathesis (RCM)—with optional labels/handles and a fit-for-purpose QC strategy. We focus on manufacturable designs: staple placement/spacing, sequence risk (aggregation/isomers), purification feasibility, and deliverables aligned to your application (screening vs assay-grade).
Stapling reinforces α-helical geometry to support function and target engagement.
Constraint often improves protease resistance and performance in biological matrices.
We recommend staple type/spacing that preserves key residues and reduces manufacturability risk.
Figure: Stapled peptide synthesis—side-chain crosslinking to stabilize α-helical structure (spacing and chemistry selected per sequence).
Related services: Custom Cyclic Peptides, Peptide Modifications, Peptide Bioconjugation. For ready-made options, browse Catalog Peptides.
Common requests: MAP-2/4/8 peptide synthesis, hetero-branched peptides, multivalent ligP / probe constructs, and dendrimeric peptide designs (project-dependent).
Uses olefin-bearing non-natural residues and ring-closing metathesis to form a robust hydrocarbon staple that reinforces α-helical structure.
Side-chain amide (e.g., Lys/Asp or Lys/Glu) that provides a stable, polar constraint for helix reinforcement.
Alternative or hybrid constraints evaluated by sequence behavior and application requirements.
Stapled peptides work best when the staple reinforces helix geometry without replacing residues critical for binding. Share your target interface and peptide length, and we’ll recommend staple type and spacing (e.g., i,i+4 or i,i+7) plus a practical synthesis/purification/QC plan.
For challenging sequences, see Difficult Peptide Synthesis.
Confirm staple chemistry/spacing, substitution positions, handles, and success criteria.
Build the sequence with compatible non-natural residues and a protecting-group plan aligned to stapling.
Perform stapling (e.g., RCM) under controlled conditions, then purify and complete QC.
Stapled peptide deliverables are sequence-dependent. We recommend fit-for-purpose purity/QC targets and a purification plan aligned to staple chemistry.
For highly hydrophobic stapled peptides, we align analytical conditions to solubility and chromatographic behavior.
For conjugation-ready constructs, see Peptide Bioconjugation.
Stapled helices are frequently used to disrupt or mimic PPI interfaces (project-dependent).
Helix stabilization can support activity in challenging cellular environments.
Use stapled variants to probe structure–activity relationships and improve performance.
Also explore: Peptide Libraries and Peptide Arrays.
A stapled peptide is a conformationally constrained peptide—often α-helical—where two side chains are covalently linked to reduce flexibility, improve stability, and enhance functional binding.
RCM hydrocarbon stapling is widely used for α-helical stabilization. Lactam bridges provide a stable polar constraint. The best choice depends on your sequence, solubility needs, and target interface. We recommend a practical route and QC plan after design review.
Common α-helical spacings include i,i+3, i,i+4, and i,i+7. Selection depends on helix length, residues required for binding, and manufacturability considerations such as aggregation and isomer formation.
Stapling is typically confirmed by mass spectrometry and chromatographic behavior. When needed, additional analyses can be used for isomeric complexity or structure-sensitive applications.
Yes. Depending on chemistry and sequence, we can incorporate biotin, fluorophores, isotope labels, and functional handles (azide/alkyne click, cysteine).
Provide your sequence, preferred staple type/spacing (or ask us to recommend), any modifications/handles, target quantity, and intended application.
Share your sequence(s), preferred staple chemistry/spacing (or “recommend”), any modifications/handles, quantity, and intended application. We’ll propose practical specifications and a synthesis/purification/QC plan aligned to your goals.
Tip: If you’re converting a linear helix to a stapled design, tell us which residues must remain unchanged and your assay buffer constraints.
The references below provide background on stapled peptide design, α-helical stabilization, and protein–protein interaction targeting. They are optional reading and not required to request a custom synthesis.
Our team applies these principles with a manufacturing focus—selecting stapling strategies that balance activity, stability, and synthesis feasibility.
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