Design, synthesis and biological evaluation of novel peptides with anti-cancer and drug resistance-reversing activities.

Chemotherapy is an important approach used to treat cancer, but severe side effects and emerging drug resistance restrict its clinical application. In this present study, we found that peptide B1 showed specific cytotoxicity to tumor cells. Moreover, a helix-wheel plot predicted that the Ser14 in this peptide is located at the interface of the hydrophobic and hydrophilic faces of B1. Subsequently, we wondered whether replacing Ser14 would alter the activity of B1, and so a series of B1 analogs were synthesized where the Ser14 was replaced by amino acids with distinct physicochemical properties. Amongst them, peptides where Ser14 was substituted by a nonpolar and basic amino acid had improved anti-cancer activity. Further investigations revealed that B1 and its analogs were capable of penetrating into cytoplasm and triggering cytochrome C release from mitochondria, which ultimately resulted in apoptosis. Meanwhile, B1 and its analogs inhibited the migration of cancer cells. The peptides also acted against drug-resistant cells and had drug resistance-reversing effects. In conclusion, these peptides might be promising candidates for oncotherapy.