Targeting intracellular protein-protein interactions with cell-permeable cyclic peptides

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Drug Discovery

Background:

• Intracellular protein-protein interactions (PPIs) are difficult targets for traditional drugs.
• Small molecules lack affinity for large PPI sites, and antibodies cannot enter cells.

Purpose of the Study:

• To review recent developments in cell-permeable cyclic peptides for targeting intracellular PPIs.
• To highlight advances in cyclic peptide design, synthesis, and membrane permeability.

Main Methods:

• Development of cyclic peptide library technologies for discovering potent ligands.
• Engineering cyclic peptides for enhanced membrane permeability via passive diffusion and active transport.
• Integration of permeability-enhancing elements into cyclic peptide design.

Main Results:

• Cyclic peptides (700-2000 MW) possess suitable size and conformational properties for PPI targeting.
• Library technologies enable rapid discovery of specific cyclic peptide ligands.
• Cell-permeable cyclic peptides are increasingly effective against intracellular PPIs.

Conclusions:

• Cell-permeable cyclic peptides represent a viable modality for targeting intracellular PPIs.
• Ongoing research focuses on optimizing design and delivery for therapeutic applications.
• This approach expands the druggable proteome for challenging diseases.