Cyclic Peptides Synthesis

Creative Peptides provides a wide range of cyclic peptide synthesis, which play a key role in different processes and have good therapeutic potential because they have several favorable properties, such as displaying a large surface area, which leads to high affinity and selectivity for protein targets, as well as their limited conformational flexibility, reducing entropy penalties during binding, thus improving their binding performance.

Application of Cyclic Peptides

• Cyclic peptides are useful in the development of peptides, toxins and drugs for therapeutic research from diagnosis to immunosuppression.
• Cyclic peptides are stable peptide analogs with strong conformational stability and biostability.
• Cyclic peptides have better biological activities and overcome linear peptide-related challenges in many cases, such as poor oral availability, membrane permeability and metabolic stability.
• Cyclic peptides can simulate the structure of bioactive peptides and bind to drug targets in vivo.
• Structural studies of peptides
• Investigation of peptides and their biological function
• Cyclic peptides have longer acting depot effects than their corresponding linear counterparts

Depending on the cyclization position, there are several methods to synthesize cyclic peptides: head-to-tail, side-chain-to-side-chain, head-to-side-chain, and side-chain-to-tail, head-to-backbone, backbone-to-tail, side-chain-to-backbone, backbone-to-side-chain. (see figure below). While head-to-tail cycles are usually formed by amide bond formation, side-chain-to-side-chain cycles are most often synthesized via Cys-Cys or amide bond formation.

Creative Peptides provides different methods for the synthesis of cyclic peptides:

Backbone Cyclization

Backbone cyclic peptides are easily assembled via the formation of an amide bond between the peptides own N-terminus amine and C-terminus carboxylic acid. Our commonly used methods are chemical synthesis and biosynthesis. Creative Peptides perform the reaction with very high yields, and routinely provide over 98% purified cycled peptides.

Side-chain Cyclization

Side chain-to-side chain cyclization is frequently employed to stabilize and select specific conformations and to reduce susceptibility toward proteolytic degradation. Creative Peptides have the capable to selectively protect, and then deprotect peptide sidechains to allow for the formation of lactam bridges between Lysine or Diaminopropanoic acid, and Glutamic and Aspartic Acids. Creative Peptides can even perform multiple different sites for bridge formation.

Disulfide-rich Peptides

Disulfide bonds are widely present in hormones, enzymes, and immunoglobulins, and are thought to play an important role in reconstructing the conformation of biologically active peptides. To further enhance biological activity, people often introduce disulfide bonds to modify bioactive peptides. Creative Peptides usually add two cysteine residues to the peptide sequence, and the dilute solution of the peptide undergoes mild oxidation to form the desired intramolecular disulfide bond between the two cysteine residues. Ugi reaction also can be provided.

Hydrocarbon-Stapled Peptide

Disulfide bonds can be easily reduced to their acyclic mercaptan form in the intracellular environment. This challenge can be overcome by hydrocarbon-bound peptide synthesis, which can form a stable α-helix structure. It can mimic the typical molecular structure at the protein-protein interaction interface. When locked in this stable configuration, the constrained peptides can penetrate the cell and act on the protein targets in the cell.

Creative Peptides provides high-quality customized peptide synthesis services

• TAT peptide synthesis
• DOTAGA chelating peptide synthesis
• Synthesis of head-to-tail cyclic peptides
• Bicyclic peptides synthesis service
• Customized synthesis of ADC molecules (solid phase synthesis+liquid phase synthesis)

Creative Peptides has successfully synthesized the target molecules needed by customers through SSPS.

Fig. 3 Typical synthesis case

• Intermediate A was synthesized in 12 steps.
• Intermediate B was synthesized in 8 steps.
• The reduction of nitro group on resin and a series of subsequent reactions were successfully completed, and the target molecule was successfully obtained, and the HPLC purity was over 95%.

Our Advantages

• Highly skilled and committed scientific staff
• Excellent Cyclic Peptide synthesis service
• Free peptide consultation and design
• Superior technical support
• In quantities of several milligrams up to 100 grams
• Quality assurance: At each stage of the production cycle, MALDI-TOF mass spectrometry and HPLC analysis are used to check the quality of each peptide.

Reference

1. Tang, J., He, Y., Chen, H., Sheng, W., & Wang, H. (2017). Synthesis of bioactive and stabilized cyclic peptides by macrocyclization using C (sp 3)–H activation. Chemical science, 8(6), 4565-4570.