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Drug Design advanced

Peptide-Protein Stapling

Chemical stapling of peptides to proteins for enhanced stability, cell penetration, and target binding.

By Encyclopeptide Editorial | 1 min read
stapling protein stability cell-penetration therapeutic

Overview

Peptide-protein stapling involves covalently linking peptide segments to protein scaffolds to create constrained, stable chimeric molecules with enhanced therapeutic properties.

Stapling Approaches

Chemical Crosslinking

  • Disulfide bonds
  • Thioether bonds
  • Click chemistry

Backbone Cyclization

  • Head-to-tail cyclization
  • Side-chain to side-chain
  • Stapled secondary structures

Benefits

  • Increased proteolytic stability
  • Enhanced cell membrane penetration
  • Pre-organized binding conformation
  • Improved receptor selectivity
  • Extended half-life

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