Bis‐Lactam Peptide [i, i + 4]‐Stapling

Summary of main observation and conclusion Even though the bis‐lactam peptide stapling with the [ i , i + 7] and the [ i , i + 11] systems has been known to be able to afford % α‐helicity values up to 100% (25°C), the performance of the bis‐lactam peptide stapling with the [ i , i + 4] system in current literature has been mediocre (% α‐helicity ≦40%, 25°C). In the current study, we found that high % α‐helicity is also obtainable with the bis‐lactam [ i , i + 4]‐stapling by demonstrating with our model peptide sequence that the bis‐lactam [ i , i + 4]‐stapling with N ε ‐ para ‐phenylenediacetyl‐lysine was able to afford a % α‐helicity value of ~64.1% (25°C). Therefore, the bis‐lactam [ i , i + 4]‐stapling could also be an efficacious peptide stapling mode that can be employed for biomedical applications.