Disulfide-rich Cyclic Peptides Synthesis Services

Among the variety of post-translational modifications (PTMs), the disulfide bond has gained considerable momentum in biological chemistry as it occurs instantaneously through oxidative folding in peptides, proteins, hormones, enzymes, growth factors, toxins, and immunoglobulins. A group of different disulfide-rich cyclic peptides has become a new focus of study in drug discovery and development field in recent years. These cyclic peptides provide an ideal scaffold for potential therapeutics.

Fig.1 The structure of two disulfide-rich peptides: α-Defensin 6 and Chlorotoxin

Disulfide-rich cyclic peptides and their disulfide bonds often have the following advantages:

• Disulfide bond cyclization improves the potency, rigidity, target selectivity, and stability of proteases
• Disulfide bond stabilizes the secondary structure of peptides
• As a common structural motif in therapeutically active compounds and nonribosomal natural products, disulfides have important biological activities
• Disulfide-rich cyclic peptides have exciting potential as leads or frameworks in drug discovery

Cyclic peptide synthesis has proven to be useful for several applications:

• Structural studies of peptides
• Investigation of peptides and their biological function
• Enzyme function and kinetics

Synthesis strategy

The artificial formation of disulfide bridges requires the proper management of cysteine residues, including first protecting and then later removing side groups and properly pairing the cysteine residues. Cysteine is the prevailing site for covalent PTM in peptides and proteins.

Fig. 2 The formation of disulfide bond (Olivier Cheneval et al, 2014)

Available Disulfide-rich cyclic peptides Synthesis Serivices

Creative Peptides provides multiple methods for synthesizing disulfide-rich cyclic peptides:

• Classical peptide synthesis (solution phase, solid phase, or native chemical ligation) followed by oxidation
  > 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)
• Ugi multicomponent reaction (U-MCR)
  We provide peptides with up to 4 disulfide bonds in one peptide.

Creative Peptides specialized in the custom synthesis of disulfide-rich cyclic peptides, providing a confidential and efficient service at competitive prices. Every step of peptide synthesis is subject to Creative Peptides' stringent quality control. Typical delivery specifications include:

• HPLC chromatogram
• Mass spec analysis
• Synthesis report
• Certificate of Analyses

References

1. Olivier Cheneval et al. Fmoc-based synthesis of disulfide-rich cyclic peptides. J. Org. Chem., 2014. 79 (12), 5538-5544.
2. Knud J. Jensen et al. Peptide Synthesis and Applications (Second Edition). 2013, 89-93.
3. Thimmalapura M. Vishwanatha et al. Sulfur-Switch Ugi Reaction for Macrocyclic Disulfide-Bridged Peptidomimetics. Org. Lett. 2017, 19, 3195-3198