Peptide Synthesis Services

Designed for biological research and industrial applications, not intended for individual clinical or medical purposes.

What is Peptide Synthesis?

Peptide synthesis is the process of synthesizing peptides, short sequences of amino acids (AAs) linked by peptide bonds, using chemical or biological methods. Peptides have an important role in signaling, enzyme function, and protein structure, making this a crucial step in biochemistry and molecular biology. An important tool in biochemistry, peptide synthesis allows for the mass creation of specific peptide sequences for applications ranging from fundamental science to drug discovery. The exploration of peptides' biological roles and potential therapeutic uses is made possible by ongoing improvements in synthesis methods, which increase the efficiency and breadth of peptide synthesis.

Why is Peptide Synthesis so Important?

Peptides are increasingly applied across biomedical, pharmaceutical, and cosmetic industries. From insulin and GLP-1 analogues to COVID-19 peptide vaccines, peptides have achieved significant success in therapeutic fields such as metabolism, oncology, and infection, and have also found extensive use in cosmetics and tissue repair materials. Their unique properties make them essential components in therapeutic drugs, vaccines, and various functional products. However, when the peptide sequence exceeds 30 amino acids, or requires cyclization or modification, synthesis challenges often arise, including incomplete condensation, accumulation of by-products, and incorrect conformations. Particularly during large-scale synthesis, yields can drop sharply, and purification becomes an extremely difficult task, almost like finding a needle in a haystack.

Creative Peptides, with its advanced high-throughput solid-phase/liquid-phase hybrid platform, real-time online monitoring technology, and kilogram-scale purification lines, routinely delivers various peptides, including linear peptides, cyclic peptides, antigen peptides, and isotopically labeled peptides. This platform allows Creative Peptides to effectively address the common synthesis traps, providing high-quality peptide synthesis services for both research institutions and pharmaceutical companies. Whether facing complex structural designs or large-scale synthesis needs, Creative Peptides offers precise solutions, making the production of high-purity peptides more efficient and greatly advancing scientific research and drug development.

Our Peptide Synthesis Services

Creative Peptides offers top-notch, professional, and swift peptide services, ensuring high-quality solutions for your research needs with precision, expertise, and unparalleled efficiency. We can offer include peptide design, synthesis, conjugation, modification, and a range of peptide-related custom services, all compliant with cGMP requirements, tailored to meet specific customer needs efficiently.

Custom Peptide Design

We offer tailored peptide design services, creating sequences to meet specific research needs. This service is ideal for drug development, vaccine research, and protein interaction studies. It helps clients design peptides with targeted functions, improving their ability to develop novel therapeutics and diagnostic tools.

Custom Peptide Synthesis

Our custom peptide synthesis service provides high-quality peptides of various lengths and complexities. Suitable for pharmaceutical research, antibody development, and vaccine creation, this service helps clients synthesize peptides with high purity and precision, supporting their research and development processes.

Amino Acid Synthesis

We offer custom amino acid synthesis, providing both standard and specialized amino acids. This service supports peptide synthesis and protein research in fields such as drug development and molecular biology. It addresses the challenge of obtaining specific amino acids for complex peptides and proteins.

Dipeptide Synthesis

Our dipeptide synthesis service provides efficient production of standard and custom dipeptides. Used in drug discovery, protein function studies, and peptide therapeutics, it helps clients synthesize functional dipeptides for applications in biomedical research and therapeutic development.

Tripeptide Synthesis

We specialize in tripeptide synthesis, providing high-quality peptides for protein research, immunology, and drug development. This service helps clients overcome challenges in synthesizing complex tripeptides, aiding in their applications in functional research, antibody development, and therapeutic research.

Branched Peptides Synthesis

Our branched peptide synthesis service specializes in complex branched peptides. This service supports research in immunology, peptide vaccines, and drug delivery systems, enabling clients to create peptides with advanced structures for targeted therapeutic applications and novel drug development.

Macrocyclic Peptides Synthesis

We offer macrocyclic peptide synthesis for applications in drug discovery and cancer immunotherapy. This service helps clients produce cyclic peptides with enhanced stability and bioactivity, advancing the development of innovative treatments and biologics with higher therapeutic potential.

Peptidomimetics Service

Our peptidomimetics service focuses on designing and synthesizing peptide-like molecules. It is ideal for drug discovery, disease treatment, and molecular recognition. This service addresses the instability and degradation of peptides by offering stable, bioactive mimetics for therapeutic and diagnostic applications.

Chemical Methods of Peptide Synthesis

Liquid-Phase Peptide Synthesis (LPPS)

This traditional technique entails the synthesis of peptides in solution. AAs are amalgamated in a liquid medium, frequently necessitating many purification stages following each coupling. Although less frequently employed than SPPS for large-scale synthesis, it might be advantageous for generating longer peptides or when handling delicate chemicals. LPPS is characterized by more homogeneous reaction conditions, as the reagents are well-mixed in solution. However, this approach faces challenges such as the difficulty in purifying intermediate products, as the peptide remains in solution throughout the synthesis. Despite this, LPPS is useful for synthesizing longer peptides or those requiring higher reaction volumes. It can also facilitate the incorporation of large or difficult-to-couple residues. The method is often applied in laboratory settings where small quantities of peptides are required and where high precision in sequence is essential.

Solid-Phase Peptide Synthesis (SPPS)

It is a method for producing various synthetic chemicals by performing chemical transformations on a solid substrate using a linker. SPPS allows for the assembly of peptides by the sequential coupling of AAs in a step-by-step fashion from the N-terminus to the C-terminus, with the C-terminus linked to a solid support. Ensuring the inclusion of one AA per step during peptide elongation requires masking the N-α- AA side chains with stable protecting groups. The last step involves releasing the peptide from the resin while simultaneously removing the side-chain protective groups. It is possible to filter out any soluble chemicals from the peptide-solid support matrix during peptide synthesis and wash them away after each coupling step. This setup allows for the completion of coupling reactions with a substantial excess of reagents at high concentrations, and the execution of all synthesis stages in a single vessel without the need to shift materials.

Automated Peptide Synthesis

Automated peptide synthesis is an efficient and precise method that is typically based on the principles of SPPS. This technique uses automated equipment to carry out the stepwise assembly of peptide chains, with precise control over the addition of each amino acid and the deprotection process. The automation reduces human error and ensures consistent reaction conditions, making it suitable for high-throughput peptide production. One of the key advantages is the ability to perform multiple synthesis steps within a single reaction vessel, eliminating the need to transfer materials and minimizing the risk of cross-contamination. Automated peptide synthesis is widely used in drug development, custom peptide production, and screening for antibody drugs. However, challenges may arise when synthesizing longer peptides or those with complex structures, particularly in terms of product purification and side-product removal.

Automated peptide synthesis using solid-phase reactors.Fig.1 Solid-phase reactors for automated peptide synthesis1,2.
Solid-phase peptide synthesis approaches: linear vs. convergent strategies.Fig.2 Solid-phase peptide synthesis strategies with linear and convergent synthesis3,4.

Biological Methods of Peptide Synthesis

Direct Extraction Method

The direct extraction method refers to obtaining peptides directly from natural sources, such as tissues, cells, or bodily fluids, through extraction and purification processes. This method typically involves breaking down biological samples to isolate peptides of interest, often using techniques like chromatography, ultrafiltration, or solvent extraction. Direct extraction is particularly valuable for obtaining peptides that are biologically active or naturally occurring, such as those with pharmaceutical or therapeutic properties. This approach can provide access to complex peptides that might be difficult or costly to synthesize chemically. However, it often faces challenges in terms of yield, purity, and the complexity of the biological matrix from which the peptides are extracted. The method is especially relevant for bioactive peptides used in drug discovery, functional foods, and nutraceuticals.

Microbial Fermentation Method

Microbial fermentation involves the use of microorganisms, such as E. coli, yeast, or actinomycetes, to produce peptides on a large scale. This method uses genetic engineering to insert the gene encoding the target peptide into the microorganism's genome, allowing the microorganism to grow and express the peptide in fermentation tanks. The main advantages of microbial fermentation are high yield and low production cost, making it ideal for large-scale peptide and protein production. This technique is commonly used for the production of simple, stable peptides and therapeutic proteins, such as recombinant insulin and antibodies. Microbial fermentation is scalable, making it suitable for industrial production. However, challenges include ensuring proper peptide folding, purifying the peptide from fermentation by-products, and optimizing fermentation conditions to achieve maximum yield and quality.

Enzymatic Peptide Synthesis

Enzymatic peptide synthesis is a biocatalytic method that utilizes enzymes, such as proteases and ligases, to catalyze peptide bond formation. This method is based on the natural enzymatic ability to join amino acids or peptides through specific peptide linkages. Enzyme-driven synthesis offers several advantages, including high specificity, mild reaction conditions, and a reduced need for toxic chemicals, making it environmentally friendly. This approach is especially effective for synthesizing peptides with complex sequences, post-translational modifications, or non-natural amino acids that are difficult to produce using traditional chemical methods. Additionally, enzymatic synthesis allows for the creation of cyclic peptides and peptide mimetics, making it useful in pharmaceutical and bioengineering applications. However, challenges include the limited range of enzymes available for different types of peptide sequences and the need for optimization of reaction conditions.

Gene Recombination Method

Gene recombination is a technique used to produce peptides by inserting the gene encoding the target peptide into the genome of a host cell, such as E. coli, yeast, or mammalian cells. The host cells then express and secrete the target peptide. This method is particularly advantageous for producing longer or more complex peptides that may be difficult to synthesize using traditional chemical methods. Gene recombination is commonly used in the production of peptide-based therapeutics, such as insulin, hormones, and antibodies. It offers high yield and the ability to produce peptides with post-translational modifications. However, challenges such as selecting the right host cell, ensuring proper peptide folding, and optimizing expression conditions must be addressed. Additionally, purification of the expressed peptide can be complex and costly.

Protein Degradation Method

Protein degradation methods, such as the native chemical ligation and expressed protein ligation (EPL) techniques, are used to produce peptides by cleaving larger proteins into smaller peptide fragments. This approach typically involves synthesizing one portion of the peptide, followed by cleavage or degradation of the protein backbone to release the desired peptide sequence. Protein degradation offers a way to produce peptides that are difficult to synthesize chemically by overcoming sequence limitations. The methods can also incorporate natural post-translational modifications that are challenging to achieve through traditional peptide synthesis techniques. However, they often require a greater level of protein purification and may be less efficient for shorter peptides. These techniques are particularly useful for producing peptides in the context of biological systems or for the synthesis of larger peptides, where high yield and specificity are critical.

Get Your Custom Quote Today!

Our team is ready to provide you with a personalized quote based on your specific peptide synthesis needs. Whether it's a standard peptide or a complex sequence with special modifications, we will work closely with you to ensure that all your requirements are met.

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Peptide Synthesis Services Workflow

1

Project Consultation & Requirement Analysis

We begin by understanding your exact research goals. Our peptide chemists work closely with you to:

  • Evaluate your peptide sequence and structure requirements
  • Recommend optimal modifications (e.g., phosphorylation, acetylation, PEGylation)
  • Discuss purity levels, scale, and intended application (in vitro, in vivo, diagnostic, etc.)

2

Peptide Design & Feasibility Assessment

Using advanced bioinformatics tools, we conduct:

  • Solubility and hydrophobicity assessment
  • Structural modeling for cyclic peptides or stapled peptides
  • Verification of modification compatibility with synthesis protocols

3

Solid Phase Peptide Synthesis

We employ Fmoc/t-Bu SPPS technology, leveraging:

  • Automated synthesizers for consistency and scalability
  • High-throughput workflows for peptides up to 100+ amino acids
  • Specialized chemistries for non-standard amino acids and linkers

4

Purification & Quality Control

Your peptide is purified via:

  • Reverse-phase HPLC (typically ≥95% purity unless otherwise requested)
  • Analytical verification through MALDI-TOF MS, LC-MS, and NMR if applicable
  • Customized QC reports, including chromatograms and MS data

5

Lyophilization, Packaging & Delivery

Once QC is complete, peptides are:

  • Lyophilized into stable powder form
  • Packaged in airtight, light-resistant vials under nitrogen
  • Shipped globally with temperature-controlled logistics (dry ice or ambient, as needed)

6

Post-Delivery Support & Re-Synthesis

We don't stop at delivery. Our support includes:

  • Guidance on peptide solubilization and buffer compatibility
  • Troubleshooting for bioassay or conjugation challenges
  • Convenient re-ordering options for recurring peptides
  • Re-synthesis with custom modifications if your needs evolve

Peptide Synthesis Applications

(1) Therapeutics: A variety of therapeutic peptides are employed to address ailments including diabetes (e.g., insulin), cancer (e.g., specific hormone analogs), and autoimmune disorders. These peptides frequently mimic or obstruct biological processes.

(2) Biomarkers: Peptides are frequently utilized in tests (e.g., ELISA) to identify particular antibodies or proteins in patient samples.

(3) Research tool: Synthetic peptides can investigate protein-protein interactions, aiding in the elucidation of signaling networks and biological processes.

(4) Antibody production: Peptides are utilized to produce particular antibodies for research purposes, facilitating the detection and quantification of target proteins.

(5) Nanotechnology: Peptides can be linked to nanoparticles or other delivery vehicles to improve the targeted administration of medicines. Peptides are employed in the creation of sensitive materials that may alter their characteristics in reaction to stimuli (e.g., pH, temperature).

(6) Cosmetics: Peptides are incorporated into skincare products to promote collagen synthesis, reduce wrinkles, and improve skin elasticity, offering anti-aging benefits.

Applications of synthetic peptides in various fields.Fig.3 Synthetic peptide-based applications5,6.
Peptide synthesis and its usefulness in various applications.Fig.4 Peptide synthesis has proven to be useful for several applications.

Why Choose Creative Peptides?

We can assist customers in selecting the appropriate peptide sequence, purity and quantity suitable for your needs. Each step of peptide synthesis is subject to Creative Peptides' stringent quality control. Typical delivery specifications include:

Case Highlights: Peptide Synthesis Services

Case 1: High-Complexity Custom Synthesis of a Multi-Modified Signal Peptide

Project Background

The client team planned to conduct a functional validation study based on signal-transduction mechanisms, requiring a medium-length peptide sequence containing multiple modification sites. The sequence included phosphorylation sites, hydrophobic segments, and a terminal fluorescent label, all of which imposed elevated requirements for structural integrity, consistency, and purity. The client expected high-quality samples within a defined timeline to support downstream assay development.

Technical Challenges

  • The sequence contained three phosphorylated amino acids, influencing both coupling efficiency and deprotection conditions.
  • The hydrophobic segment resulted in insufficient intermediate solubility, increasing the difficulty of chain elongation.
  • The C-terminus required the incorporation of a highly stable fluorescent tag, creating additional demands for purification control and final structural verification.

Solution

The project team developed a differentiated strategy tailored to the sequence characteristics:

  • Optimized coupling pathways at critical sites and applied a high-activity condensation system to enhance elongation efficiency.
  • Implemented staged solvent-system switching for the hydrophobic region to stabilize the reaction environment of intermediates.
  • Adopted customized protection strategies during the terminal labeling step to secure the structural integrity of the fluorescent moiety.
  • Used dual analytical methods (HPLC and MS) to monitor each critical stage, ensuring overall process controllability.

Deliverables

  • Successfully obtained the target peptide meeting the client's quality specifications.
  • All modification sites were structurally verified, with high labeling efficiency and stability aligned with client expectations.
  • Delivery lead time was shortened by approximately 20% compared with standard approaches.
  • Provided a complete QC data package for direct integration into downstream functional workflows.

Client Feedback

The client team endorsed the overall delivery quality, highlighting significant advantages in managing complex modification architectures and in project communication efficiency. Based on this experience, they plan to initiate long-term collaboration across multiple parallel sequences.

Case 2: Custom Synthesis of a Highly Hydrophobic Peptide

Project Background

The client required a 45-residue peptide sequence containing over 60% hydrophobic amino acids to study protein–membrane interactions. The sequence's high hydrophobicity posed solubility challenges, while maintaining structural integrity was essential for downstream biophysical assays. The client needed a reproducible synthesis protocol capable of reliably delivering ≥50 mg per batch for iterative experiments.

Technical Challenges

  • High hydrophobic residue content caused poor intermediate solubility, increasing aggregation and chain deletion risks, especially after 25–30 residues.
  • Standard HBTU/DIEA coupling protocols were insufficient for the extended sequence length, requiring enhanced elongation strategies.
  • The sequence was sensitive to standard TFA-based deprotection, risking partial cleavage or modifications of side-chain protecting groups (e.g., tBu on Ser/Thr, Trt on Cys).

Solution

  • Employed a stepwise solvent-switching approach using DMF/NMP and 10% DMSO for particularly hydrophobic segments to stabilize intermediates.
  • Used HATU/DIPEA activation with double-coupling cycles at critical junctions to enhance elongation efficiency.
  • Applied mild TFA/TIS deprotection at 25 ℃ with continuous HPLC/MS monitoring to ensure sequence fidelity.
  • Introduced temporary pseudoproline dipeptides at positions 12–13 and 28–29 to reduce aggregation during elongation.

Deliverables

  • Successfully synthesized the 45-residue hydrophobic peptide, delivering ≥50 mg per batch with verified sequence integrity.
  • Optimized process ensured reproducible yields across three consecutive synthesis batches.
  • Provided complete QC reports, including HPLC/MS spectra for each key elongation step, enabling immediate use in biophysical assays.

Client Feedback

The client appreciated the team's expertise in managing highly hydrophobic sequences, noting significantly improved batch consistency and reduced chain deletion. They plan to expand collaboration for additional long-sequence peptide projects.

Case 3: Site-Specific Fluorescent Labeling of a Therapeutic Peptide

Project Background

The client requested a 28-residue therapeutic peptide with a single fluorescent dye conjugated to a Lys side chain at position 18 for real-time cellular tracking. Maintaining peptide stability and ensuring precise dye incorporation were critical to avoid impacting biological activity.

Technical Challenges

  • Site-specific labeling risked incomplete conjugation or unintended reactions at N-terminal or other Lys residues.
  • Fluorescent dyes were sensitive to TFA and basic conditions, necessitating precise handling during cleavage and purification.
  • Purification was complicated by residual unreacted dye and truncated sequences, requiring high-resolution separation.

Solution

  • Employed orthogonal protecting groups: Fmoc-Lys(Mtt) at position 18 for selective deprotection and labeling.
  • Optimized labeling conditions using 1.2 eq of a fluorescent dye NHS ester in DMF with DIEA at room temperature for 2 h to maximize conjugation efficiency while preserving peptide stability.
  • Applied semi-preparative RP-HPLC with a C18 column (250 × 10 mm, 5 µm) and MS verification to separate labeled product from by-products.
  • Conducted intermediate QC at each stage using LC-MS to confirm mass and labeling completion.

Deliverables

  • Delivered ≥20 mg of site-specifically labeled peptide with verified structure and high stability.
  • Achieved labeling efficiency of >95% with minimal side-products.
  • Provided full QC package, including HPLC chromatograms and MS spectra, for direct use in cellular imaging studies.

Client Feedback

The client highlighted the high precision and reliability of the labeling workflow. They noted that the rapid, reproducible process would allow scaling to additional therapeutic peptide candidates with multiple labeling sites.

Frequently Asked Questions

What is peptide synthesis, and why is it important?

Peptide synthesis is the process of creating peptides, which are short chains of amino acids linked by peptide bonds. Peptides play essential roles in biological processes, such as cell signaling, immune response, and enzyme activity. Synthetically produced peptides are critical for research, drug discovery, diagnostics, and therapeutic applications.

References

  1. Image retrieved from Figure 1 "Comparison of solid-phase reactors for automated peptide synthesis", Sletten, Eric T., et al., 2019, used under [CC BY 3.0] (https://creativecommons.org/licenses/by/3.0/). The title was changed to "Solid-phase reactors for automated peptide synthesis".
  2. Sletten, Eric T., et al., Real-time monitoring of solid-phase peptide synthesis using a variable bed flow reactor., Chemical Communications 55.97 (2019): 14598-14601. https://doi.org/10.1039/C9CC08421E
  3. Image retrieved from Figure 1 "Solid-phase peptide synthesis strategies", Bédard, François, and Eric Biron., 2018, used under [CC BY 4.0] (https://creativecommons.org/licenses/by/4.0/). The title was changed to "Solid-phase peptide synthesis strategies with linear and convergent synthesis".
  4. Bédard, François, and Eric Biron., Recent progress in the chemical synthesis of class II and S-glycosylated bacteriocins., Frontiers in Microbiology 9 (2018): 1048. https://doi.org/10.3389/fmicb.2018.01048
  5. Image retrieved from Graphical abstract, Yang, Shihua, et al., 2023, used under [CC BY 4.0] (https://creativecommons.org/licenses/by/4.0/). The title was changed to "Synthetic peptide-based applications".
  6. Yang, Shihua, et al., Self-assembled short peptides: Recent advances and strategies for potential pharmaceutical applications., Materials Today Bio 20 (2023): 100644. https://doi.org/10.1016/j.mtbio.2023.100644

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