Cyclic Peptide Synthesis
Custom Cyclic & Macrocyclic Peptides — From Disulfide to Click Chemistry
Boston Molecules specializes in custom cyclic peptide synthesis with multiple cyclization chemistries. From simple disulfide bridges to advanced click chemistry and RCM — we deliver research-grade macrocyclic peptides with confirmed structural characterization.
⚡ Get Instant Quote Browse CatalogWhy Cyclic Peptides?
Druglike Properties
Cyclic peptides occupy a unique chemical space between small molecules and biologics. Cyclization enables oral bioavailability (Cyclosporine A paradigm) and cell permeability.
Conformational Constraint
Pre-organizing the peptide backbone reduces entropic penalty upon target binding, increasing affinity by 10–1000× compared to linear counterparts.
Clinical Momentum
30+ cyclic peptides approved or in Phase 3. RaPID (Peptidream), bicyclic peptides (Bicycle Therapeutics), and macrocyclic PPI inhibitors are reshaping the pipeline.
Cyclization Chemistries We Offer
Head-to-Tail (Backbone) Cyclization
N-terminus to C-terminus amide bond forming a macrocyclic ring. The gold standard for conformational constraint. Dramatically improves metabolic stability and oral bioavailability.
Example: Cyclosporine A, SFTI-1
Disulfide-Bridged Cyclization
Intramolecular S–S bond between two cysteine residues. The most common natural cyclization strategy. Found in hormones, toxins, and defensins.
Example: Oxytocin, Somatostatin, α-Conotoxins
Lactam-Bridged Cyclization
Sidechain-to-sidechain amide bond, typically between Lys (ε-NH₂) and Asp/Glu (γ/δ-COOH). Highly stable, non-reducible alternative to disulfide bridges.
Example: MT-II, PT141 (Bremelanotide)
Thioether (Lanthionine) Cyclization
C–S bond between Cys thiol and dehydro-amino acid. Found in lantibiotics. Provides irreversible constraint with excellent stability in reducing environments.
Example: Nisin, Duramycin
Click Chemistry (Triazole) Cyclization
Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) forming a 1,2,3-triazole linkage. Biorthogonal, highly chemoselective, and tolerates diverse functional groups.
Example: Triazole-stapled peptides
RCM (Ring-Closing Metathesis)
Olefin metathesis between allyl-glycine or pentenyl-alanine residues. Creates carbon–carbon crosslinks. Used in both stapled and macrocyclic peptide design.
Example: HBS α-helices, cRGD variants
Linear vs. Cyclic Peptide Properties
| Property | Linear Peptide | Cyclic Peptide | Improvement |
|---|---|---|---|
| Protease Resistance | ★☆☆☆ | ★★★★ | 10–1000× improvement |
| Target Affinity | ★★☆☆ | ★★★★ | Pre-organized binding conformation |
| Selectivity | ★★☆☆ | ★★★★ | Reduced off-target binding |
| Cell Permeability | ★☆☆☆ | ★★★☆ | Passive diffusion (Rule of 5 compliant) |
| Oral Bioavailability | ☆☆☆☆ | ★★★☆ | Cyclosporine A paradigm |
| Serum Half-life | ★☆☆☆ | ★★★☆ | Minutes → hours |
Research & Therapeutic Applications
| Application Area | Key Targets | Approach |
|---|---|---|
| Oncology 🔥 Hot | RAS, p53-MDM2, PD-1/PD-L1, BCL-2 | PPI disruption, intracellular targets |
| Infectious Disease | Gram-positive bacteria, HIV, HCV | Antimicrobial cyclic peptides, protease inhibitors |
| Metabolic Disease 🔥 Hot | GLP-1R, GIPR, Ghrelin receptor | Orally bioavailable peptide agonists |
| CNS / Pain | Opioid receptors, ion channels | BBB-penetrant constrained peptides |
| Dermatology | Integrins, MC1R | Topically active macrocycles |
| Peptide Drug Discovery 🔥 Hot | mRNA display, phage display libraries | Cyclic peptide screening platforms (e.g., RaPID) |
Our Cyclic Peptide Platform
Cyclization Methods
- ✅ Head-to-tail backbone cyclization
- ✅ Disulfide bridge formation (single & multiple)
- ✅ Lactam bridge (Lys-Asp/Glu sidechain)
- ✅ Thioether / lanthionine linkage
- ✅ Click chemistry (CuAAC triazole)
- ✅ Ring-closing metathesis (RCM)
QC & Characterization
- ✅ HPLC purity analysis (>95%)
- ✅ LC-MS / MALDI-TOF mass confirmation
- ✅ Ellman's test (free thiol confirmation)
- ✅ CD spectroscopy (helicity, if applicable)
- ✅ Scale: mg to multi-gram
- ✅ GMP-compatible process development
Custom Peptide Synthesis Quote
Design your custom peptide and get an instant quote with our online configurator.
⚡ Get Instant QuoteFor research use only. Not for diagnostic or therapeutic use.