Stapled Helical Peptides Bearing Different Anchoring Residues

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Structural Biology

Background:

• Protein-protein interactions (PPIs) are crucial biological processes.
• Peptides are promising inhibitors for PPIs but face stability and cell permeability challenges.
• Stapled helical peptides enhance stability and membrane permeability compared to linear peptides.

Purpose of the Study:

• To review peptide stapling techniques for chemical, biophysical, and biological applications.
• To provide a comprehensive inventory of anchoring residues for peptide stapling.
• To guide the rational design of stapled peptides as therapeutics for PPIs.

Main Methods:

• Categorization of anchoring residues (natural, nonnatural, or combined).
• Discussion of various peptide stapling methodologies and their advantages.
• Analysis of factors influencing stapled peptide biophysical properties.

Main Results:

• Stapled peptides exhibit improved proteolytic stability and membrane permeability.
• Different anchoring residues and cross-linker strategies impact peptide properties.
• Specific stapling techniques offer advantages like reversibility and photoisomerization.

Conclusions:

• Peptide stapling is a versatile strategy for developing stable and cell-penetrant peptide inhibitors.
• Rational design considering anchoring residues and staple features is key for therapeutic applications.
• Stapled peptides hold significant therapeutic potential for targeting protein-protein interactions.