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Published on: January 26, 2016
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Targeting intracellular protein-protein interactions with macrocyclic peptides
1Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA.
Trends in Pharmacological Sciences
|December 16, 2021
Summary
Macrocyclic peptides (MPs) are promising inhibitors of intracellular protein-protein interactions (PPIs). Recent advances enable cell-permeable MPs to target these challenging PPIs within cells, opening new therapeutic avenues.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Intracellular protein-protein interactions (PPIs) are critical biological processes but challenging drug targets.
- Traditional drugs struggle to inhibit intracellular PPIs due to cell membrane impermeability.
- Macrocyclic peptides (MPs) show potential as PPI inhibitors but face delivery challenges.
Purpose of the Study:
- To review recent advancements in developing cell-permeable macrocyclic peptides.
- To highlight strategies for overcoming MP cell membrane impermeability.
- To discuss the therapeutic potential of intracellularly acting MPs.
Main Methods:
- Review of scientific literature on macrocyclic peptide development and cell permeability.
- Analysis of mechanisms for MP cellular entry, including passive diffusion and endocytosis.
- Discussion of rational design and screening approaches for MP discovery.
Main Results:
- Significant progress has been made in designing 'drug-like' MPs.
- Cell-permeable MPs can potently and specifically modulate intracellular PPI targets.
- Multiple mechanisms for MP cellular entry are being elucidated.
Conclusions:
- Cell-permeable macrocyclic peptides represent a promising new modality for targeting intracellular PPIs.
- Overcoming cell membrane barriers is key to realizing the therapeutic potential of MPs.
- Continued research in MP science will advance the development of novel therapeutics for challenging diseases.
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