Peptidomimetics Targeting Protein-Protein Interactions for Therapeutic Development
Gan Zhang1,2, Jessica Andersen1, Guillermo Gerona-Navarro1,2,3
1Department of Chemistry, Brooklyn College, 2900 Bedford Avenue, Brooklyn, NY 11210, United States.
Protein and Peptide Letters
|November 2, 2018
Summary
Peptidomimetics offer a promising solution for targeting challenging protein-protein interactions (PPIs). These molecules mimic peptides but have improved drug-like properties, advancing treatments for diseases caused by dysfunctional PPIs.
Area of Science:
- Medicinal Chemistry
- Drug Discovery
- Biochemistry
Background:
- Protein-protein interactions (PPIs) are crucial for cellular functions; their dysregulation causes diseases.
- Targeting PPIs is difficult due to their large, flat surfaces, often considered 'undruggable' by small molecules.
- Peptides are effective at targeting PPIs but suffer from poor pharmacokinetic properties.
Purpose of the Study:
- To explore peptidomimetics as a viable alternative to traditional small molecules and peptides for targeting PPIs.
- To highlight the development of chemically modified peptides with enhanced therapeutic potential.
Main Methods:
- Development of chemical approaches to create conformationally constrained peptides.
- Focus on methods like stapled peptides and large-scale macrocyclizations.
- Evaluation of peptidomimetics for improved pharmacokinetic profiles.
Main Results:
- Peptidomimetics retain the structural features of peptides while exhibiting improved pharmacokinetic properties.
- Chemically modified peptides demonstrate enhanced stability and bioavailability.
- Successful application of these molecules in targeting various biological systems.
Conclusions:
- Peptidomimetic molecules represent a promising therapeutic strategy for targeting pathogenic PPIs.
- Advancements in chemical synthesis enable the development of effective peptidomimetic drugs.
- These novel therapeutics hold significant potential for treating currently incurable human diseases.
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