Stapled Peptide Design

Stapled Peptide Design

Peptide stapling is a strategy for constraining short peptides typically in an alpha-helical conformation. Stapling is carried out by covalently linking the side-chains of two amino acids, thereby forming a peptide macrocycle. Peptide “stapling” via interside-chain hydrocarbon linkages has emerged as one of the most promising approaches for the generation of potent and stable type Ⅰ peptidomimetics of α-helical protein binding motifs. Once inside the cell, stapled peptides are stable, and able to initiate or inhibit protein-protein interactions that are useful for the treatment of cancer, insulin secretion, inflammation and many other disease states.

Advantages of stapled peptides in drug design

The introduction of a hydrocarbon staple confers high levels of α-helical content and results in:

Better target affinity (5 to 5,000-fold increase)

Targeting of either extracellular or intracellular proteins

Viable pharmacokinetics and in vivo stability

Disruption of protein-protein interactions

Cell penetration through endocytic vesicle trafficking

Increased proteolytic resistance and serum half-life

Non-immunogenicity

Available Stapled Peptide Design Services

Creative Peptides provides multiple methods for synthesizing stapled peptides.

Grubbs catalysts are routinely used in olefin metathesis to incorporate hydrocarbon staples into peptides.

The high efficiency and mild conditions of “click” reaction (Copper-catalyzed Huisgen 1,3-dipolar cycloaddition reaction) combined with the ease of synthesis of the necessary unnatural amino acids, allows for facile synthesis of triazole-stapled peptides.

UV-induced reaction between tetrazoles and alkenes has been used by Madden et al. to staple peptides for inhibition of the p53-MDM2/MDMX interaction.

Creative Peptides has extensively developed stapled peptide structures and is the company of choice to manufacture your stapled peptide requirements, 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

FAQs

Stapled peptides are short amino acid sequences that form stable, helical structures due to covalent side-chain linkages. They are essential in research for mimicking protein-binding motifs and modulating protein interactions, which helps in studying cellular processes and disease mechanisms.

Stapling enhances the peptide's helical stability, improving its binding affinity and ability to disrupt protein interactions. This makes stapled peptides effective tools for studying protein signaling and cellular functions.

Stapled peptides offer enhanced target affinity, better stability, and improved cell penetration. They are non-immunogenic and can target both extracellular and intracellular proteins, making them highly versatile for various research applications.

Stapled peptides are synthesized using techniques like Grubbs catalysts in olefin metathesis or copper-catalyzed click chemistry. These methods ensure efficient peptide formation and enable precise targeting of specific protein interactions.

Creative Peptides is a trusted provider of stapled peptide design, offering efficient and high-quality services at competitive prices. We provide detailed reports, including HPLC chromatograms and mass spectrometry analysis, to ensure the highest standards of peptide synthesis.

Clients receive comprehensive reports including HPLC chromatograms to confirm purity, mass spectrometry analysis to verify molecular weight, and a synthesis report outlining the peptide production process.

References

Zhang, H., Curreli, F., Waheed, A. A., Mercredi, P. Y., Mehta, M., Bhargava, P & Summers, M. F. (2013). Dual-acting stapled peptides target both HIV-1 entry and assembly. Retrovirology, 10(1), 136.

Tan, Y. S., Lane, D. P., & Verma, C. S. (2016). Stapled peptide design: principles and roles of computation. Drug Discovery Today, 21(10), 1642-1653.

Lau, Y. H., De Andrade, P., Wu, Y., & Spring, D. R. (2015). Peptide stapling techniques based on different macrocyclisation chemistries. Chemical Society Reviews, 44(1), 91-102.