Macrocyclic modification of peptidomimetics can fully combine the advantages of small molecules and biotherapeutics, with synthetic accessibility, low immunogenicity and toxicity, high selectivity, and the ability to target protein surfaces. CD BioSciences provides comprehensive peptidomimetic cyclization services, and customers can choose the appropriate cyclization method according to their specific requirements.
Overview of Macrocyclization
Macrocyclization makes peptides and peptidomimetics more stable and can increase membrane permeability, making them an important medicinal chemistry strategy in peptide drug development. There are several traditional methods of peptide cyclization, such as amide formation, but before the desired intramolecular reaction occurs, a defined precyclized conformation must be formed, which is an entropically unfavorable process. The same is true for head-to-tail cyclization and results in extension of the peptide precursor. Peptides can also cyclize side chains, especially in applications that stabilize secondary structures, such as alpha-helices and beta-sheets, resulting in so-called "stapled peptides".
Fig. 1 Internal thiazole-directed peptide modification and macrocyclization. (Cai, et al., 2022)
Advantages of Macrocyclized Peptidomimetics
Peptides are a growing class of therapeutics because of their unique spatial features that can target protein-protein interactions and surfaces that have traditionally been "untreatable". Despite their advantages, peptides must overcome several key disadvantages to be considered drug leads, including their high conformational flexibility and susceptibility to proteolytic cleavage. Peptidomimetics are often developed to improve these properties, with linear peptidomimetics modified by macrocyclization being more desirable.
Fig. 2 Synthesis of peptidomimetic 76 on an industrial scale with RCM as a key transformation for closing the macrocycle. (Bechtler, C., & Lamers, C., 2021)
Our Services
CD BioSciences offers comprehensive peptidomimetic macrocyclization services. Our PepDomTM platform can carry out a full range of cyclization design and cyclization peptidomimetics development, whether it is challenging head-to-tail cyclization, side chain cyclization and other bond cyclizations, we are committed to meeting the research needs of our customers.
Our services include but are not limited to the following:
- Sulfur-mediated amide formation
- Other functional groups-mediated amide formation
- Macrocyclization employing imines and oximes
- Amine-reactive stapling
- Thioether formation cyclization
- Scaffold thioether formation
- Scaffold-mediated cyclization of thiol and amine
- C-C bond formation cyclization
- C–C single bond formation: CH-Activation, etc.
- C–C double bond formation: alkene metathesis
- C–C triple bond formation: ring-closing alkyne metathesis
- Disulfide cyclization
- Triazole formation cyclization
- Thioacetal formation cyclization
Features of Our peptidomimetics
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| Synthesis Accessibility |
Low Toxicity |
High Binding Affinity |
Better Membrane Permeability |
| Design and synthesis are carried out by a professional platform and scientific research team. |
Unfavorable sequences or fragments have been altered or eliminated. |
The design of the specific conformation enables better binding to the target site. |
The introduction of the ring structure increases the stability across the membrane. |
CD BioSciences is specialized in providing various services for the development of peptidomimetics. We are committed to providing comprehensive peptidomimetic cyclization modification services. In addition to higher stability, the cyclized peptidomimetics have also improved their affinity and membrane permeability. As long as you are interested in any aspect of peptidomimetic development, please contact us for the best solution.
References
- Cai, C., Wang, F., Xiao, X., Sheng, W., Liu, S., & Chen, J., et al. (2022). Macrocyclization of bioactive peptides with internal thiazole motifs via palladium-catalyzed C-H olefination. Chemical Communications. 58(31), 4861-4864.
- Bechtler, C., & Lamers, C. (2021). Macrocyclization strategies for cyclic peptides and peptidomimetics. RSC Medicinal Chemistry, 12(8), 1325–1351.
All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
