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Updated: Jun 14, 2025
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Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
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Enhancing cyclic peptide functionality with hydrophilic diamino acids for improved APC-Asef interaction inhibition
Shipeng He1, Jie Zhong2, Ziqiang Yu3
1School of Medicine or Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Shanghai Engineering Research Center of Organ Repair, Shanghai 200444, China.
Bioorganic & Medicinal Chemistry
|June 12, 2025
Summary
Novel diamino acids enhance cyclic peptide stability and solubility, improving inhibition of protein-protein interactions (PPIs). This strategy offers a promising therapeutic approach for metastatic colorectal cancer.
Area of Science:
- Medicinal Chemistry
- Peptide Therapeutics
- Oncology
Background:
- Cyclic peptides are effective protein-protein interaction (PPI) inhibitors.
- Traditional disulfide bonds in cyclic peptides lead to instability and reduced activity.
- Metastatic colorectal cancer presents a significant therapeutic challenge.
Purpose of the Study:
- To develop a novel strategy for constructing stable and soluble cyclic peptides.
- To enhance the inhibitory activity of peptide-based therapeutics.
- To explore new therapeutic agents for metastatic colorectal cancer.
Main Methods:
- Synthesis of cyclic peptides using novel hydrophilic diamino acids.
- Application of the diamino acid strategy to the APC-Asef PPI inhibitor MAI-516.
- Comparative analysis of diamino acid-based cyclic peptides versus disulfide bond-based cyclic peptides.
Main Results:
- Diamino acid-based cyclic peptides demonstrated improved aqueous solubility and stability.
- Enhanced inhibitory activity against APC-Asef PPI was observed.
- The novel strategy effectively overcomes limitations of traditional disulfide bond-based cyclic peptides.
Conclusions:
- Novel hydrophilic diamino acids provide a robust strategy for peptide cyclization.
- This approach enhances peptide stability, solubility, and biological activity.
- The developed cyclic peptides show potential as therapeutic agents for metastatic colorectal cancer.
