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Peptides And Proteins
Application scenarios cover new hot spots and valuable research fields, such as protein purification and detection, disease-related research, immunology and biochemistry research, scientific research peptides, medicinal peptides, etc., to meet the needs of researchers at different stages. We have a complete customer service system and technical team, each peptide product purified by HPLC, more stable quality, more timely delivery.
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Cyclic Peptides

Cyclic Peptides

Detailed Introduction


KS-V Peptide team can effectively overcome the difficulties of ring formation and folding of cyclic peptides and disulfide-rich polypeptides,and has successfully synthesized polypeptides rich in 4 pairs of disulfide bonds with physiological functions, and even achieved the synthesis of 7 pairs of disulfide bonds.
 
Peptides have various structures, including chain polypeptides, cyclic peptides, etc. Because chain polypeptides are so flexible that they can be twisted and flipped at will, making them too loose to work well as drugs. By introducing a cyclic structure, the researchers constrain the activity of the peptide, increase the stability of the peptide, make it show better pharmacological activity and stability, and make it possible for more peptides to be made into drugs. Cyclic peptides combine the advantages of small molecules and biological macromolecules. They not only have strong targeting and affinity similar to macromolecular antibody drugs, but also have the ability to rapidly penetrate into tissues similar to small molecule drugs. Due to its unique structure and activity, cyclic peptides are favored by pharmaceutical companies, but compared with chain peptides, cyclic peptides are more difficult to form into rings and fold, and require higher synthesis techniques.
 
Cyclic peptides are commonly used for diagnostics and vaccine development. Compared with straight-chain peptides, cyclic peptides have better conformational stability, target affinity, and improved selectivity. KS-V now offers compressive types of cyclic peptides up to g levels to help accelerate your peptide therapeutic development projects.
 
 
                         Cyclic Peptides
 
 
New drugs based on cyclic peptides are entering the market, such as plecanatide, a cyclic peptide approved by the United States Food and Drug Administration in 2017 for the treatment of chronic idiopathic constipation. These have widespread applications for clinical and research purposes: imaging, diagnostics, improvement of oral absorption, enzyme inhibition, development of receptor agonist/antagonist, and the modulation of protein-protein interaction or protein-RNA interaction. Many cyclic peptides are expected to emerge as therapeutics and biochemical tools.
 
                           Cyclic Peptides
 
 
 
Backbone to backbone cyclization strategies through the formation of an amide bond between the N-terminal and C-terminal amino acid residues.
Cyclization of side chain amino acids such as:

  • Formation of disulfide bridges between cysteine (homocycsteine)
  • Formation of lactam bridges between glutamic/aspartic acid and lysine residues
  • Formation of lactone and thiolactone bridges between amino acid containing carboxyl, hydroxyl or mercapto functional groups.
  • Formation of thioether or ether bridges between the amino acids containing hydroxyl or mercapto functional groups and other special methods.

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 (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.
 
                                Cyclic Peptides

 

Disulfide Bridge Cys-Cys Thiol Oxidation

 
Peptide disulfide bridge readily synthesizes two thiol (SH) groups from the side chain of cysteine or cysteine analogs. Our unique synthesis strategy enables us to offer either specific intra or intermolecular oxidation using appropriate protecting group chemistry to prevent undesired linkage. The reaction can be followed by HPLC and MALDI TOF mass spectrometry with the linear peptide losing two mass units (2H) on cyclization.
 
In General, disulfide bridge can be formed as follows:
 
Intermolecular (two peptide molecules are linked via the disulfide bridge), resulting in either:
homodimers (two identical peptides) or
heterodimers (two different peptides).
Intramolecular (cyclization within one peptide molecule)
While head-to-tail cyclization is usually formed by using an amide bond formation, side-chain-to-side-chain peptide cyclization is most often synthesized via cys-cys or amide bond formation.
 
Peptide cyclization using cys-cys has limited stability in reductive conditions. Therefore, projects involving drug discovery, commonly use cys-cys cyclized peptides for initial screening and optimization followed by replacement of disulfide bonds with more stable bonds.
 
Peptides with two or more disulfide bridges require selective protection of the cysteine side chains to ensure that the correct disulfide bridges are formed. We provide peptides with up to 4 disulfide bonds in one peptide using site-specific orthogonal chemistry or thermodynamic stability methods. Contact us to discuss your project details.

 

Amide Bond formation, Lactam Formation

 
Cyclic peptides can also be synthesized by linking the amino (N) terminus of the peptide to the carboxyl (C) terminus via an amide bond. The amino side chains of Lys and Orn and the carboxyl side chains of Asp and Glu can also be used to construct cyclic peptides via an amide bond. Amide bonds are more chemically stable than disulfide bridge. Depending on functional groups of a peptide, cyclic peptide synthesis can be formed in four different ways:
 
Head-to-tail between N-terminus and C-terminus
Head-to-side chain between N-terminus and an internal COOH (e.g. the ß-COOH-group of Asp or γ-COOH-group of Glu)
Side chain-to-tail between internal NH2s and C-terminus (e.g. the ε-NH2–group of Lys)
Side-chain-to-side-chain between an internal NH2 and an internal COOH (e.g. the ε-NH2–group of Lys with either the ß-COOH-group of Asp or γ-COOH-group of Glu)
As with disulfide cys-cys cyclization, amide cyclization is also limited by the challenges of dimerization, undesirable side reactions such as racemization or peptide capping by coupling reagents. For an effective head-to tail cyclization, it is important to carefully select cyclization site, reagent, and optimized cyclization conditions. Biosynthesis has extensive experience in synthesizing amide cyclic peptides with a high success rate.

 

Stapled Peptide Synthesis

 
Cysteines are common structural motifs in naturally occurring peptides such as neurotoxins, somatostatin and insulin. These disulfide bridges are readily reduced to their acyclic thiol form in an intracellular environment. This challenge can be overcome by using hydrocarbon-stapled peptide synthesis. These peptides are capable of forming stable alpha helical structures as a result of “hydrocarbon stapling" . Stapled peptides have a chemically locked conformational structure which can mimic the molecular structures that are typically found at the interface of protein-protein interactions. When locked into this stable configuration, constrained peptides are able to penetrate cells and can exert their effect on intracellular protein targets. The large surface area of peptides gives them an advantage over small molecules in their ability to disrupt specific signaling pathways by inhibiting targeted protein-protein interactions. Hydrocarbon stapling is a useful strategy in researching experimental and therapeutic modulation of protein-protein interactions as well as in-vivo pharmacokinetics studies.
 
                                 Cyclic Peptides

 

Click Chemistry for peptide cyclization

 
The cyclization technique increases peptide molecules' potency and in vivo half-life by locking their conformation. In addition to disulfide and amide cyclizations, many other cyclization methods are available at Bio-Synthesis. Clickable functional groups can be incorporated into synthesized peptides using different combinations of protected amino acids modified with an alkyne group, followed by a click reaction with an azido acid. The resulting peptides are detached from the resin to give triazole-containing peptides. Post-synthesis modification allows the introduction of these functional groups to produce structurally constrained peptides. Bio-Synthesis scientists have used click reactions to prepare several different peptide cyclizations.
 
 
                               Cyclic Peptides
 
 
 
 
 
 

 

Products
Peptides And Proteins
Application scenarios cover new hot spots and valuable research fields, such as protein purification and detection, disease-related research, immunology and biochemistry research, scientific research peptides, medicinal peptides, etc., to meet the needs of researchers at different stages. We have a complete customer service system and technical team, each peptide product purified by HPLC, more stable quality, more timely delivery.
Home >

products >

Cyclic Peptides

Cyclic Peptides

Detailed Introduction


KS-V Peptide team can effectively overcome the difficulties of ring formation and folding of cyclic peptides and disulfide-rich polypeptides,and has successfully synthesized polypeptides rich in 4 pairs of disulfide bonds with physiological functions, and even achieved the synthesis of 7 pairs of disulfide bonds.
 
Peptides have various structures, including chain polypeptides, cyclic peptides, etc. Because chain polypeptides are so flexible that they can be twisted and flipped at will, making them too loose to work well as drugs. By introducing a cyclic structure, the researchers constrain the activity of the peptide, increase the stability of the peptide, make it show better pharmacological activity and stability, and make it possible for more peptides to be made into drugs. Cyclic peptides combine the advantages of small molecules and biological macromolecules. They not only have strong targeting and affinity similar to macromolecular antibody drugs, but also have the ability to rapidly penetrate into tissues similar to small molecule drugs. Due to its unique structure and activity, cyclic peptides are favored by pharmaceutical companies, but compared with chain peptides, cyclic peptides are more difficult to form into rings and fold, and require higher synthesis techniques.
 
Cyclic peptides are commonly used for diagnostics and vaccine development. Compared with straight-chain peptides, cyclic peptides have better conformational stability, target affinity, and improved selectivity. KS-V now offers compressive types of cyclic peptides up to g levels to help accelerate your peptide therapeutic development projects.
 
 
                         Cyclic Peptides
 
 
New drugs based on cyclic peptides are entering the market, such as plecanatide, a cyclic peptide approved by the United States Food and Drug Administration in 2017 for the treatment of chronic idiopathic constipation. These have widespread applications for clinical and research purposes: imaging, diagnostics, improvement of oral absorption, enzyme inhibition, development of receptor agonist/antagonist, and the modulation of protein-protein interaction or protein-RNA interaction. Many cyclic peptides are expected to emerge as therapeutics and biochemical tools.
 
                           Cyclic Peptides
 
 
 
Backbone to backbone cyclization strategies through the formation of an amide bond between the N-terminal and C-terminal amino acid residues.
Cyclization of side chain amino acids such as:

  • Formation of disulfide bridges between cysteine (homocycsteine)
  • Formation of lactam bridges between glutamic/aspartic acid and lysine residues
  • Formation of lactone and thiolactone bridges between amino acid containing carboxyl, hydroxyl or mercapto functional groups.
  • Formation of thioether or ether bridges between the amino acids containing hydroxyl or mercapto functional groups and other special methods.

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 (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.
 
                                Cyclic Peptides

 

Disulfide Bridge Cys-Cys Thiol Oxidation

 
Peptide disulfide bridge readily synthesizes two thiol (SH) groups from the side chain of cysteine or cysteine analogs. Our unique synthesis strategy enables us to offer either specific intra or intermolecular oxidation using appropriate protecting group chemistry to prevent undesired linkage. The reaction can be followed by HPLC and MALDI TOF mass spectrometry with the linear peptide losing two mass units (2H) on cyclization.
 
In General, disulfide bridge can be formed as follows:
 
Intermolecular (two peptide molecules are linked via the disulfide bridge), resulting in either:
homodimers (two identical peptides) or
heterodimers (two different peptides).
Intramolecular (cyclization within one peptide molecule)
While head-to-tail cyclization is usually formed by using an amide bond formation, side-chain-to-side-chain peptide cyclization is most often synthesized via cys-cys or amide bond formation.
 
Peptide cyclization using cys-cys has limited stability in reductive conditions. Therefore, projects involving drug discovery, commonly use cys-cys cyclized peptides for initial screening and optimization followed by replacement of disulfide bonds with more stable bonds.
 
Peptides with two or more disulfide bridges require selective protection of the cysteine side chains to ensure that the correct disulfide bridges are formed. We provide peptides with up to 4 disulfide bonds in one peptide using site-specific orthogonal chemistry or thermodynamic stability methods. Contact us to discuss your project details.

 

Amide Bond formation, Lactam Formation

 
Cyclic peptides can also be synthesized by linking the amino (N) terminus of the peptide to the carboxyl (C) terminus via an amide bond. The amino side chains of Lys and Orn and the carboxyl side chains of Asp and Glu can also be used to construct cyclic peptides via an amide bond. Amide bonds are more chemically stable than disulfide bridge. Depending on functional groups of a peptide, cyclic peptide synthesis can be formed in four different ways:
 
Head-to-tail between N-terminus and C-terminus
Head-to-side chain between N-terminus and an internal COOH (e.g. the ß-COOH-group of Asp or γ-COOH-group of Glu)
Side chain-to-tail between internal NH2s and C-terminus (e.g. the ε-NH2–group of Lys)
Side-chain-to-side-chain between an internal NH2 and an internal COOH (e.g. the ε-NH2–group of Lys with either the ß-COOH-group of Asp or γ-COOH-group of Glu)
As with disulfide cys-cys cyclization, amide cyclization is also limited by the challenges of dimerization, undesirable side reactions such as racemization or peptide capping by coupling reagents. For an effective head-to tail cyclization, it is important to carefully select cyclization site, reagent, and optimized cyclization conditions. Biosynthesis has extensive experience in synthesizing amide cyclic peptides with a high success rate.

 

Stapled Peptide Synthesis

 
Cysteines are common structural motifs in naturally occurring peptides such as neurotoxins, somatostatin and insulin. These disulfide bridges are readily reduced to their acyclic thiol form in an intracellular environment. This challenge can be overcome by using hydrocarbon-stapled peptide synthesis. These peptides are capable of forming stable alpha helical structures as a result of “hydrocarbon stapling" . Stapled peptides have a chemically locked conformational structure which can mimic the molecular structures that are typically found at the interface of protein-protein interactions. When locked into this stable configuration, constrained peptides are able to penetrate cells and can exert their effect on intracellular protein targets. The large surface area of peptides gives them an advantage over small molecules in their ability to disrupt specific signaling pathways by inhibiting targeted protein-protein interactions. Hydrocarbon stapling is a useful strategy in researching experimental and therapeutic modulation of protein-protein interactions as well as in-vivo pharmacokinetics studies.
 
                                 Cyclic Peptides

 

Click Chemistry for peptide cyclization

 
The cyclization technique increases peptide molecules' potency and in vivo half-life by locking their conformation. In addition to disulfide and amide cyclizations, many other cyclization methods are available at Bio-Synthesis. Clickable functional groups can be incorporated into synthesized peptides using different combinations of protected amino acids modified with an alkyne group, followed by a click reaction with an azido acid. The resulting peptides are detached from the resin to give triazole-containing peptides. Post-synthesis modification allows the introduction of these functional groups to produce structurally constrained peptides. Bio-Synthesis scientists have used click reactions to prepare several different peptide cyclizations.
 
 
                               Cyclic Peptides