Résumé
We previously demonstrated that the NC1[α3(IV)185–191] CNYYSNS peptide inhibited in vivo tumor progression. The YSNS motif formed a β turn crucial for biological activity. The aim of the present study was to design a YSNSG cyclopeptide with a constrained β turn on the YSNS residues more stable than CNYYSNS. By nuclear magnetic resonance and molecular modeling, we demonstrated that the YSNSG cyclopeptide actually adopted the expected β-turn conformation. It promoted melanoma cell adhesion and prevented their adhesion to the native peptide. It inhibited in vitro cell proliferation and migration through Matrigel by downregulating proteolytic cascades. Moreover, intraperitoneal administration of the YSNSG cyclopeptide inhibited melanoma progression far more efficiently than the native peptide. The increased solubility and stability at low pH of the YSNSG cyclopeptide suggest this peptide as a potent antitumor therapeutic agent.