Peptides as drugs: from screening to application.

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology
• Drug Discovery

Background:

• Proteins form complex networks with numerous interaction partners.
• Protein-protein interactions are crucial for cellular functions.
• Hot spots mediate a significant portion of binding energy in protein interactions.

Purpose of the Study:

• To review the potential of peptides as therapeutic agents.
• To highlight peptides that inhibit protein-protein interactions.
• To discuss methods for peptide selection, optimization, and delivery.

Main Methods:

• Peptide selection using display technologies (phage, ribosome, yeast) and yeast-two-hybrid system.
• Peptide optimization via peptide arrays.
• Stabilization using non-natural amino acids (peptidomimetics), lipocalins, and peptide aptamers.
• Strategies for intracellular delivery (carrier systems, protein transduction domains, gene therapy).

Main Results:

• Peptides can mimic natural ligands and modulate protein activity.
• Targeting protein-protein interaction hot spots offers a therapeutic strategy.
• Various methods exist for developing and delivering peptide-based drugs.

Conclusions:

• Peptides show significant potential as drugs, particularly for inhibiting protein-protein interactions.
• Advances in peptide design and delivery enhance their therapeutic applicability.
• Peptide therapeutics offer a promising avenue for treating diseases driven by aberrant protein interactions.