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Beschreibung

A cell-permeable, hexapeptide containing a novel integrin-binding motif, SDV (a Type I PDZ-binding motif) that is shown to compete with vitronectin for the RGD-binding site of integrin alphavbeta3 (IC50 = 1.74 pg/ml), in a chip-based assay. It is rapidly internalized into HUVECs, but not in NIH 3T3 cells, at a culture temperature of 37 C, a process which is mediated by caveolin and clathrin. At 10 µ,g/ml, this compound is shown to significantly inhibit the phosphorylation of ERK1/2 and MEK in HUVECs. Furthermore, it suppresses bFGF-induced proliferation of HUVECs, dose-dependently, and displays up-regulation of p53 and induction of apoptosis via activation of caspases-3, -8 and -9 at 50 µ,g/ml.