Long & High-Complexity Peptide Synthesis

Custom long and high‑complexity peptide synthesis for sequences that exceed routine SPPS.

Failed elsewhere?
Enzymatic synthesis (expression-based)
50–200+ aa
High‑complexity sequences
Fragments + ligation chemistry
HPLC/MS + COA

Need something ready-made? Browse Catalog Peptides.

Long Peptides Built for High Complexity

Long peptides and high-complexity sequences often exceed the limits of routine solid-phase peptide synthesis (SPPS). As sequence length and structural propensity increase, on-resin aggregation, reduced chain mobility, and difficult motifs can lower coupling efficiency, amplify truncation impurities, and compromise reproducibility.

Bio-Synthesis, Inc. specializes in sequence-aware long peptide synthesis for targets that resist conventional workflows. Rather than relying on extended coupling cycles alone, we apply deliberate aggregation control, strategic motif planning, and route selection tailored to sequence behavior.

Depending on the target, synthesis may involve optimized single-chain SPPS, fragment-based assembly with ligation chemistry (e.g., native chemical ligation), or enzymatic synthesis (expression-based) approaches for very long or hybrid constructs. Each project is reviewed by experienced peptide scientists to select a strategy that balances purity, yield, reproducibility, and analytical confidence for the intended application.

Long peptides (50–200+ aa)

Sequence-defined targets for immunology, vaccines, and mechanistic studies.

  • Route selection based on sequence behavior
  • Purification strategy aligned to acceptance criteria
  • COA with analytical results
Difficult peptide “rescue”

For peptides that fail routine SPPS at other vendors.

  • Aggregation hotspot assessment
  • Targeted mitigation strategies
  • Fragment pathways when needed
Ligation & expression options

When chemical synthesis alone is not the best solution.

  • Fragment assembly + ligation chemistry
  • Protein expression for very long targets
  • Hybrid route proposals (project-dependent)

Why Long Peptide Synthesis Becomes Difficult

Long peptide synthesis challenges are usually driven by sequence behavior, not length alone. The most common failure mechanism is on-resin aggregation, which reduces chain mobility and coupling efficiency, increasing deletion/truncation impurities and lowering crude quality.

Aggregation & secondary structure
  • Hydrophobic stretches
  • β-sheet propensity
  • “Silent” coupling losses
Steric & motif effects
  • Repetitive motifs
  • Polybasic stretches
  • Sequence-specific hindrance
Complexity features
  • Multiple cysteines / disulfides
  • Labile residues or modifications
  • Heterogeneity risks

Tip: If you have prior HPLC/MS traces or notes about solubility/aggregation, include them—this helps us select the most reliable route.

Long Peptide Workflow

A long peptide project typically moves through design review, synthesis/assembly, purification, and QC. Highly challenging targets may use fragment assembly and ligation chemistry, or an expression-based route for very long sequences.

1) Design review
  • Aggregation hotspot assessment
  • Route selection: SPPS vs fragments vs expression
  • Define acceptance criteria and QC endpoints
2) Build & deliver
  • Optimized synthesis and/or fragment production
  • Assembly/ligation as needed
  • Purification + HPLC/MS + COA

Optional project elements (as needed): additional characterization, alternative salt forms, and documentation upgrades.

Synthesis Strategy Overview

Long peptide synthesis routes are selected based on sequence behavior rather than length alone. Manageable sequences may be completed as a single chain, while aggregation-prone targets benefit from fragment-based assembly and ligation chemistry.

Single-chain SPPS
  • Optimized coupling cycles
  • Aggregation-aware planning
  • Simpler purification path
Fragment-based assembly
  • Strategic fragment breakpoints
  • Ligation chemistry (e.g., NCL)
  • Improved control for difficult motifs
Diagram comparing single-chain SPPS and fragment-based peptide assembly with ligation chemistry

Figure: Long peptide synthesis routes — single-chain SPPS vs fragment assembly with ligation chemistry.

Route Options: SPPS, Ligation Chemistry, and Protein Expression

We recommend the simplest route that reliably meets your targets. Some long peptides can be completed by optimized SPPS, while others benefit from fragment assembly and ligation chemistry. For very long targets or peptide–protein constructs, expression-based routes may be more practical.

Optimized SPPS
  • Cycle tuning for difficult regions
  • Aggregation-aware planning
  • Purification aligned to specs
Fragments + ligation
  • Strategic fragment breakpoints
  • Ligation chemistry (e.g., NCL)
  • Improved control for difficult motifs
Protein expression (hybrid)
  • Very long targets / domain-like constructs
  • Peptide–protein hybrids
  • Project-dependent hybrid strategies

Specifications for Long & High-Complexity Peptides

Sequence & complexity
  • Provide sequence (1-letter codes preferred)
  • Flag hydrophobic segments, repeats, or motifs
  • Specify cysteines and disulfide requirements
Purity target
  • Choose based on application and assay sensitivity
  • Long peptides may be method-limited in % purity
  • We’ll recommend practical acceptance criteria
Scale & consistency
  • mg to gram-scale (project-dependent)
  • Repeat synthesis / lot consistency options
  • Plan ahead for scale-up pathways
Modifications & labels
  • N-/C-terminal modifications
  • Labels and conjugation handles (as required)
  • Complex mods may favor fragment assembly

Also available: Catalog peptides for immediate use.

Analytics & Quality Control

Analytical testing confirms identity and supports reproducibility. For long peptides, method selection and interpretation should match the target length, composition, and application.

Standard analytics
  • HPLC purity profiling
  • Mass spectrometry identity confirmation
  • Certificate of Analysis (COA)
Optional testing
  • Amino acid analysis / composition checks
  • Counter-ion analysis (as requested)
  • Additional characterization upon request

If you share your application (screening vs quantitative assays vs regulated work), we’ll recommend the most meaningful QC endpoints.

Applications

Immunology
  • Epitope mapping constructs
  • T-cell studies
  • Antigen design projects
Vaccines
  • Long antigen peptides
  • Multi-epitope designs
  • Feasibility and validation
Mechanistic studies
  • Protein domain mimetics
  • Pathway probes
  • Binding and functional assays

How to request a quote

For the fastest quote, include the details below. If you’re unsure about purity or route, share your application and we’ll recommend a practical spec.

Include in your request
  • Sequence (1-letter codes), length, and any non-standard residues
  • Modifications/labels (with positions)
  • Desired quantity and purity/QC endpoints
  • Intended application (immunology, vaccine, mechanistic, etc.)
Helpful optional details
  • Known solubility or aggregation issues
  • Prior vendor outcomes (HPLC/MS traces)
  • Preferred counter-ion (TFA vs acetate)
  • Any documentation requirements

FAQ

What is included in the COA?

A typical COA includes identity confirmation (MS) and purity profiling (HPLC). Additional testing (e.g., counter-ion analysis or composition checks) can be added upon request.

How do you approach failed peptide synthesis for long sequences?

We start by reviewing sequence behavior and any prior data (HPLC/MS, crude purity, solubility notes). Common root causes include on-resin aggregation and reduced chain mobility. We then select the most reliable route—optimized SPPS, fragment-based assembly with ligation chemistry, or enzymatic synthesis (expression-based)—and align QC endpoints to your application.

What counts as a long peptide?

Long peptides are commonly considered >50 amino acids. However, difficulty is driven more by sequence behavior (aggregation, hydrophobicity, repeats, disulfide density) than length alone.

When do you use ligation chemistry?

Ligation chemistry (e.g., native chemical ligation) is typically used when the sequence is severely aggregation-prone, includes challenging motifs, or when a single continuous SPPS route is unlikely to meet targets.

Do you offer options?

Yes. For very long targets, peptide–protein hybrids, or domain-like constructs, expression or hybrid strategies can be more reliable than purely chemical synthesis. We’ll recommend the best route based on your requirements.

What purity should I request for a 100–200 aa peptide?

Purity is method-dependent and can be limited by chromatographic resolution and intrinsic heterogeneity. Share your application and we’ll recommend practical acceptance criteria and QC endpoints.

Can you help if my peptide failed at another vendor?

Yes. If you share prior HPLC/MS traces, crude purity estimates, or notes about solubility/aggregation, we can recommend a targeted rescue strategy (optimized SPPS vs fragments + ligation vs expression).

How long does long peptide synthesis typically take?

Timelines depend on sequence length, complexity, and synthesis route. Optimized single-chain SPPS projects typically require several weeks, while fragment-based assembly, ligation chemistry, or enzymatic synthesis routes may require additional time for fragment preparation, assembly, purification, and analytical verification. Project timelines are confirmed after sequence review.

CONTACT US

Speak to a Peptide Scientist

Share your sequence, intended application, purity/scale needs, and any prior synthesis data. We’ll recommend a practical route and provide a quote.

Tip: If the peptide is long/hydrophobic/cysteine-rich, include that context so we can route the request to the right strategy.

Why Choose Bio-Synthesis

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