As a part of our ongoing effort in establishing the bis-lactam [i,i+4]-stapling as an efficacious peptide stapling mode that can be employed for biomedical applications,like the bis-lactam peptide [i,i+7]-and [i,i+11]-stapling,in the current study we explored the possibility of employing the D-disubstituted L-α-methylated thialysines in promoting the bis-lactam peptide [i,i+4]-stapling.