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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
Published on: January 26, 2016
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Macrocyclic peptides as protein-protein interaction modulators: a review
Erin Ann Sunny1, Sandhya Sadanandan1
1Department of Chemistry, School of Advanced Sciences, VIT-AP University, Amaravati, Andhra Pradesh 522241, India. sandhya.sadanandan@vitap.ac.in.
Organic & Biomolecular Chemistry
|April 22, 2026
Summary
Macrocyclic peptides offer a promising strategy for targeting challenging protein-protein interactions (PPIs) that are difficult for small molecules to address. These cyclic peptides are advancing precision medicine for various diseases.
Area of Science:
- Biochemistry and Molecular Biology
- Drug Discovery and Development
- Medicinal Chemistry
Background:
- Protein-protein interactions (PPIs) are crucial for cellular functions but are difficult to target with conventional drugs due to their large, dynamic interfaces.
- Macrocyclic peptides represent a novel therapeutic modality, bridging the gap between small molecules and biologics.
- Conformational constraint in peptides, achieved through natural cyclic peptides and phage display, enhances affinity and stability.
Purpose of the Study:
- To review emerging strategies for discovering macrocyclic peptide-based modulators of protein-protein interactions (PPIs).
- To highlight the application of these modulators in targeting diverse diseases, including oncology, infectious diseases, and inflammatory conditions.
- To discuss future directions in peptide-based drug development for PPIs.
Main Methods:
- Literature review of recent advancements in macrocyclic peptide drug discovery for PPIs.
- Exploration of high-throughput screening, structure-based drug design, and artificial intelligence in identifying peptide therapeutics.
- Analysis of chemical modification techniques (e.g., stapling, unnatural amino acids) to enhance peptide properties.
Main Results:
- Macrocyclic peptides demonstrate high specificity and affinity for targeting extended protein surfaces.
- Successful targeting of disease-driving PPIs like MDM2-p53, BCL-2 family, and KRAS-effector complexes is evident.
- Chemical modifications improve peptide stability, proteolytic resistance, and cell permeability.
Conclusions:
- Macrocyclic peptides are a versatile platform for developing novel therapeutics against challenging PPI targets.
- These peptide-based drugs hold significant potential for expanding precision medicine applications across various diseases.
- Continued innovation in discovery and modification techniques will drive the future of PPI-directed peptide therapeutics.
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