Custom Cyclic Peptide Synthesis

Macrocycles built for stability, binding, and real-world assay conditions.

Overview

What is a cyclic peptide?

A cyclic peptide is a peptide constrained into a ring by connecting the backbone (N-to-C head-to-tail) and/or side chains (e.g., disulfide or lactam bridges). This conformational constraint can sharpen a peptide’s bioactive shape, improving protease resistance, solution stability, and often target affinity compared with linear analogs. Cyclic and macrocyclic peptide designs are widely used in drug discovery, epitope/vaccine research, and assay development because they can better mimic structured binding motifs and retain performance in challenging matrices.

Bio-Synthesis manufactures cyclic peptides and macrocyclic peptide constructs using practical cyclization routes (head-to-tail, disulfide, lactam bridges, and stapling) with optional labels/handles (biotin, fluorophores, azide/alkyne click chemistry, cysteine handles) and a fit-for-purpose QC strategy. We don’t just “close the ring”—we engineer manufacturable designs: selecting cyclization sites, protecting-group strategy, and purification/QC to match your goal (screening, assay-grade, or immunization) and to reduce risk from aggregation, isomers, or solubility limits.

ISO 9001:2015 / ISO 13485:2016 U.S. facilities (Texas) Difficult & hydrophobic peptide expertise Custom modifications & handles
Conformational control

Ring closure can lock in bioactive shapes, improving potency and selectivity (sequence-dependent).

Higher stability

Cyclization can reduce proteolysis and increase stability in biological matrices.

Design flexibility

Supports non-natural amino acids, labels, and handles when compatible with the cyclization chemistry.

Common peptide cyclization strategies including head-to-tail cyclization, lactamisation, disulfide formation, thioether, oxime, ester, and triazole-based cyclization methods

Figure: Common peptide cyclization strategies used in custom cyclic and macrocyclic peptide synthesis.

Custom cyclic peptide synthesis Macrocyclic peptide synthesis Head-to-tail cyclization Disulfide cyclic peptides Lactam-bridged peptides Stapled peptides

Related services: Custom Peptide Synthesis, Peptide Modifications, Peptide Bioconjugation. For ready-made options, browse Catalog Peptides .

Cyclization methods we support

Head-to-tail (N-to-C)

Backbone cyclization for compact macrocycles and improved protease resistance.

  • Best for sequences with accessible termini
  • Ring size influences yield and conformation
  • Often paired with strategic spacers or turn-inducing residues
Disulfide cyclization

Cys–Cys loop formation with controlled oxidation conditions.

  • Common for looped epitopes and structured motifs
  • Optional mapping strategies for complex cystine patterns
  • Redox conditions selected to reduce scrambling risk
Lactam bridges (side-chain)

Amide bond between side chains (e.g., Lys/Asp or Lys/Glu) for robust constraints.

  • Strong conformational lock without redox sensitivity
  • Useful when termini are reserved for labels/handles
  • Bridge position tuned for target conformation
Stapled peptides (helix constraint)

Hydrocarbon stapling or related constraints for α-helical stabilization (project-dependent).

  • Improves helical propensity and cellular stability in many designs
  • Requires compatible non-natural residues / positions
  • Plan purification/QC based on hydrophobicity and isomer complexity
Bicyclic / multi-constraint designs

When needed, multiple constraints can be used to refine conformation and potency.

  • Two disulfides, disulfide + lactam, or other combinations
  • Sequence risk assessment is critical for manufacturability
  • We recommend a staged approach when complexity is high

Design guidance: de-risk cyclization early

Most cyclic peptide delays come from choosing a cyclization strategy that conflicts with sequence behavior (aggregation, sterics, or solubility). Share your goal (assay vs screening vs immunization), and we’ll recommend practical cyclization sites, ring size, and QC.

Design checklist
  • Specify cyclization type (or ask us to recommend)
  • Define cyclization sites (termini or side chains) and ring size
  • Flag sensitive residues or required PTMs/modifications
  • Decide handle placement (biotin, azide/alkyne, cysteine, dyes)
  • Set fit-for-purpose purity/QC: assay-grade vs screening-grade
Common risk factors
  • Hydrophobic stretches that reduce solubility and HPLC resolution
  • High propensity for secondary structure on-resin (aggregation)
  • Multiple cysteines (possible disulfide scrambling)
  • Very small rings (high strain) or very large rings (heterogeneity)

If your sequence is “difficult,” see Difficult Peptide Synthesis.

Non-natural amino acids PEG / spacers Biotin / fluorophores Click handles (azide/alkyne) Isotope labels

Synthesis workflow

1) Design review

Confirm cyclization route, sites, modifications/handles, and success criteria.

2) SPPS assembly

Optimized coupling strategy for difficult segments; protect groups aligned to planned closure.

3) Cyclization & finishing

Ring closure (or oxidation) under controlled conditions, followed by purification and QC.

What we optimize (practically)
  • Protecting-group strategy to prevent side reactions
  • Concentration/solvent conditions to favor intramolecular closure
  • Oxidation strategy for disulfide formation (when applicable)
  • Purification approach matched to solubility and heterogeneity
  • Analytical plan to confirm identity and cyclization
  • Documentation aligned to your downstream workflow

Specifications: what to define for a fast quote

Core specs
  • Sequence and target cyclization method (or “recommend”)
  • Cyclization sites (termini or side-chain positions)
  • Modifications/handles (biotin, dyes, azide/alkyne, cysteine)
  • Quantity (mg) and intended application
  • Purification/QC needs (desalt vs HPLC; MS; HPLC report)
Fastest quote checklist
  • One sequence per line (or attach a spreadsheet)
  • State “assay” vs “screening” vs “immunization”
  • Note solubility constraints (buffer, co-solvent limits) if known
  • Indicate required purity threshold (if strict)
  • Provide timeline and shipping requirements

Typical cyclic peptide deliverables are sequence-dependent. For constrained or highly hydrophobic designs, we recommend fit-for-purpose purity/QC targets.

Parameter Typical options Notes / guidance
Cyclization types Head-to-tail, disulfide, lactam, stapled, multi-constraint Method selection should match sequence behavior and application.
Purification Desalted or HPLC purified (where feasible) Hydrophobic or heterogeneous products may limit HPLC resolution.
QC MS identity, HPLC profile (when applicable) Additional confirmation may be used for complex disulfide patterns.
Options Non-natural AAs, PEG/spacers, labels, click handles Specify handle location and downstream chemistry to align QC.
Quantity 1–10 mg typical (more upon request) Yield depends on sequence risk and purification level.

QC & deliverables

Standard analytics
  • Mass spectrometry identity confirmation (MALDI-TOF or ESI-MS)
  • HPLC profile / purity assessment (sequence-dependent)
  • Certificate of Analysis (COA)

For peptides with disulfides, optional reduction/alkylation workflows can support confirmation when required.

Fit-for-purpose guidance
  • Assay-grade: prioritize purity and analytical clarity
  • Screening libraries: prioritize throughput and consistency
  • Immunization: identity-confirmed, practical purity target

If you need conjugation-ready cyclic peptides, see Peptide Bioconjugation.

Applications

Drug discovery

Macrocycles for target engagement, inhibitor design, and SAR optimization.

Diagnostics & assays

Stable ligands and capture reagents with defined handles (biotin, click, dyes).

Vaccine & epitope research

Constrained loops to mimic native epitopes and improve recognition.

Also explore: Peptide Arrays and Peptide Libraries.

FAQ

Which cyclization method should I choose?

The best method depends on your sequence, ring size, required conformation, and downstream use. Head-to-tail is common for backbone cyclization; disulfide is useful for cystine loops; lactam bridges add stability; stapling constrains helices. We review your design and recommend a practical route and QC plan.

Can you cyclize peptides with non-natural amino acids or labels?

Yes. We support non-natural amino acids, isotope labels, biotin, fluorescent tags, and functional handles (e.g., azide/alkyne, cysteine) when compatible with the cyclization chemistry and purification strategy.

Do cyclic peptides require purification and what purity is realistic?

Many cyclic peptides are HPLC-purifiable, but highly hydrophobic or aggregation-prone sequences may limit resolution. We align purity targets to your use case and recommend fit-for-purpose deliverables.

How do you confirm cyclization?

Cyclization is typically confirmed by mass spectrometry and chromatographic behavior. For disulfide patterns or complex conformations, additional methods (e.g., reduction/alkylation mapping or NMR) may be used when required.

What information do you need for a fast quote?

Provide your sequence, desired cyclization type (or ask us to recommend), any modifications/handles, target quantity, and intended application. If you know solubility constraints or required purity/QC, include them to speed quoting.

What is a cyclic peptide?

A cyclic peptide is a peptide whose backbone or side chains are connected to form a ring (macrocycle). Cyclization can improve conformational control, protease resistance, and functional binding depending on sequence and target.

CONTACT

Speak to a Peptide Scientist

Share your sequence(s), preferred cyclization method (or “recommend”), any modifications/handles, quantity, and intended application. We’ll propose practical specifications and a synthesis/QC plan aligned to your goals.

Tip: If you’re comparing cyclic vs linear constructs, tell us your assay conditions and solubility constraints so we can recommend the best design.

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.