Chemical Modification for Proteolytic Stabilization of the Selective α_vβ₃ Integrin RGDechi Peptide: in Vitro and in Vivo Activities on Malignant Melanoma Cells

Abstract

Herein, we report the synthesis and biological characterization of the new peptide ψRGDechi as the first step toward novel-targeted theranostics in melanoma. This pseudopeptide is designed from our previously reported RGDechi peptide, known to bind selectively α_vβ₃ integrin, and differs for a modified amide bond at the main protease cleavage site. This chemical modification drastically reduces the enzymatic degradation in serum, compared to its parental peptide, resulting in an overall magnification of the biological activity on a highly expressing α_vβ₃ human metastatic melanoma cell line. Selective inhibition of cell adhesion, wound healing, and invasion are demonstrated; near-infrared fluorescent ψRGDechi derivative is able to detect α_vβ₃ integrin in human melanoma xenografts in a selective fashion. More, molecular docking studies confirm that ψRGDechi recognizes the receptor similarly to RGDechi. All these findings pave the way for the future employment of this novel peptide as promising targeting probe and therapeutic agent in melanoma disease.