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Major obstacles in peptide-based PPI inhibitors design and the representative solutions.
| Obstacles | Solutions |
|---|---|
| Hydrophobicity | Charged/polar residues incorporation |
| Stability | Capping additions (acetylation and amidation) |
| Cyclization/disulfide bonds | |
| Hydrocarbon stapled peptides | |
| D-amino acid replacement | |
| Unnatural amino acid modifications | |
| Peptoids | |
| Renal clearance | Macromolecules/polymers conjugations |
| Permeability | Stapled peptides/cell-penetrating peptides |
