jm7b01590_si_001.pdb (924.35 kB)
Chemical Modification for Proteolytic Stabilization of the Selective αvβ3 Integrin RGDechi Peptide: in Vitro and in Vivo Activities on Malignant Melanoma Cells
dataset
posted on 2017-11-16, 00:00 authored by Daniela Comegna, Antonella Zannetti, Annarita Del Gatto, Ivan de Paola, Luigi Russo, Sonia Di Gaetano, Annamaria Liguoro, Domenica Capasso, Michele Saviano, Laura ZaccaroHerein,
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 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 ψRGDechi derivative is able to detect αvβ3 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.