50
peptides active in vitro
INCI
requirements satisfied
Non-toxic
skin-permeable peptides in vitro
90 nM
IC50 of the best peptide
01/ Background
- The target is a GPCR driving protease-induced itch and inflammation.
- The goal is to design skin-permeable linear peptide antagonist (4-10 AAs).
- Peptides must be INCI-compliant.
- No protein binders known.
02/ Methodology
- MD performed on target protein, 5 conformations were selected.
- 10 starting peptides were AI-generated inside the binding pocket.
- In-pocket peptide optimization under mutation rules aligned with INCI-requirements.
- 34 ADME-Tox and 36 PhysChem parameters computed.
- ~2K peptides were shortlisted for visual analysis.
- ~100 peptides were selected for validation.
03/ Results
- 50 peptides are active in vitro
- Skin permeability achieved for all hits.
- No toxic effect observed in vitro.
- The top hit shows IC50 90 nM.
04/ Binding pose
- The 6-mer peptide spans hydrophobic grooves and polar hotspots.
- 7 residues involved in conventional H-bonds.
- Additional π-π/σ and π-alkyl interactions complete the fit.
*Binding pose of one of the top peptides
