Cyclic Peptide Synthesis

Peptide cyclization is a common strategy to develop cyclic peptides with improved conformational stability compared to linear analogs. These cyclic peptides are useful in a variety of applications, including mimicking protein secondary structures (e.g., protein loops) and optimizing peptide ligands for improved binding potency, selectivity, and enhanced protease stability. With decades of hands-on experience in peptide synthesis and research, CD Formulation has developed specific skills and expertise that enable it to produce cyclic peptides of superior quality. We have become experts in designing and producing specialty peptides of the highest quality, even for complex or unusual peptide sequences.

What is Cyclic Peptide?

Cyclic peptides are stable peptide analogs in which the amino acid sequence forms a cyclic or ring-like structure. Cyclic peptides vary in length and are usually composed of a few to dozens of amino acids. Cyclic peptides have strong conformational stability and biological stability and are a promising emerging therapeutic drug. Compared with linear peptides, cyclic peptides have better conformational stability, target affinity, and higher selectivity. Their cyclic structure is achieved by forming a covalent bond between the first and last amino acid residues of the peptide chain, which enhances their ability to target challenging protein-protein interactions associated with various diseases.

Fig. 1 Strategies of peptide cyclization and stabilization of α-helices, β-sheets, and β-strands. (Wang L, et al., 2022)

Explore Our Custom Cyclic Peptide Synthesis Services

our team of peptide synthesis experts has the expertise and specific skills to design and synthesize high-quality cyclic peptides for a variety of applications based on your needs.

Our scientists are familiar with a variety of synthesis techniques, including solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), and chemo-enzymatic peptide synthesis (CEPS), allowing us to select the most appropriate technology to support each individual peptide synthesis project. At the same time, we strictly follow quality control standards to ensure that we provide you with high-purity, low-impurity peptide products.

Our cyclic peptide synthesis services include but are not limited to the following:

• Main-chain to main-chain cyclization is achieved by amide bond formation between N-terminal and C-terminal amino acid residues.
• Side-chain amino acid cyclization is achieved by disulfide bond formation between cysteines (homocysteine).
• Lactam bridge formation between glutamic acid/aspartic acid and lysine residues.
• Lactone and thiolactone bridge formation between amino acids containing carboxyl, hydroxyl, or sulfhydryl functional groups.
• Thioether or ether bridge formation between amino acids containing hydroxyl or sulfhydryl functional groups and other special methods.

Our Peptide Cyclization Technologies

Depending on the cyclization site, we use different cyclization techniques to synthesize cyclic peptides, including head-to-tail cyclization, side chain-to-side chain, head-to-side chain, and side chain-to-tail cyclization. Head-to-tail cyclization is usually formed via amide bond formation, while side-chain-to-side-chain cyclization is most often synthesized via Cys-Cys or amide bond formation within the cyclic peptide.

Head-to-Tail Cyclization

Head-to-tail cyclization refers to the formation of an amide bond between the N-terminus and C-terminus of a linear peptide, resulting in a cyclic peptide with increased stability. This method is often used to generate cyclic peptide libraries for screening and drug development.

Side-Chain-to-Side-Chain Cyclization

Side-chain-to-side-chain cyclization involves the formation of a bond between two amino acid side chains within a peptide. This method can be achieved through a variety of chemical reactions, including disulfide bond formation and amide bond formation.

Other Cyclization Methods

In addition to disulfide and amide cyclization, there are many other cyclization methods available. Examples include cyclization via click chemistry (copper-catalyzed azide-alkyne cycloaddition, CuAAC) or cyclization that generates thioethers, such as the cyclization of cysteine side chains via bromoacetate.

Key Cyclization Strategies

Our peptide synthesis experts usually use the following two main cyclization strategies to achieve cyclic peptide synthesis.

Cys-Cys Cyclization

Cys-Cys cyclization results from the formation of disulfide bonds between the cysteine residues of a peptide. This is the most direct and commonly used method for peptide cyclization. However, Cys-Cys cyclization is prone to dimerization as a side reaction. To address this issue, our scientists minimize this by performing the cyclization under highly diluted conditions. We have successfully synthesized peptides with up to four disulfide bonds in one peptide using site-specific orthogonal chemistry.

Amide Cyclization

As with the Cys-Cys cyclization, dimerization must be limited in the amide cyclization, which can be achieved by performing the cyclization under high dilution conditions. Since amide bonds are more stable than disulfide bonds, they are most commonly used to prepare the following types of cyclic peptides:

• Head-to-Tail Cyclic Peptide

Head-to-tail cyclic peptides are formed by linking the N- and C-termini of a linear peptide via an amide bond. This approach can improve stability and resistance to enzymatic degradation.

• Side-Chain to Side-Chain Cyclic Peptide

Side-chain-side-chain cyclic peptides are formed by linking the side chains of two amino acids within the peptide via an amide bond. This approach can generate peptides with specific conformations and properties.

Peptide Manufacturing & Analytical Services

In addition to peptide synthesis capabilities, CD Formulation combines flexible GMP manufacturing facilities with cutting-edge peptide analytical knowledge to provide a full range of quality control testing services to accelerate the commercialization of your products, including:

Publication

CD Formulation's cyclic peptide synthesis services are tailored to meet the specific needs of researchers and organizations seeking high-quality peptides for drug discovery, vaccine development, diagnostics, and other scientific endeavors. Please don't hesitate to contact us if you are interested in our services. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.