Chemical Modification for Proteolytic Stabilization of the Selective αvβ3 Integrin RGDechi Peptide: In Vitro and in Vivo Activities on Malignant Melanoma Cells

Herein, we report the synthesis and biological characterization of the new peptide φRGDechi as the first step toward novel-targeted theranostics in melanoma. This pseudopeptide is designed from our previously reported RGDechi peptide, known to bind selectively αvβ3 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 αvβ3 human metastatic melanoma cell line. Selective inhibition of cell adhesion, wound healing, and invasion are demonstrated; near-infrared fluorescent φRGDechi derivative is able to detect αvβ3 integrin in human melanoma xenografts in a selective fashion. More, molecular docking studies confirm that φRGDechi 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.