Tumor vasculatures express high levels of α(V)β(3)/α(V)β(5) and α(5)β(1) integrins. Peptide containing the RGD (Arg-Gly-Asp) sequence, which is present in ligands of integrins, is effective in targeting therapeutic reagents to tumor vascular endothelium. In this study, we investigated whether the biological activity of endostatin 27 peptides can be enhanced by the addition of an integrin targeting sequence. RGDRGD and GGGRGD sequence were added to the carboxyl terminus of endostatin 27 and 25 peptides, respectively. Modification of endostatin 27 peptides with the RGD motif showed specific and increased binding to endothelial cells and the increased binding is consistent with improved antiangiogenic property. RGD-modified endostatin 27 peptides was more effective than human endostatin and endostatin 27 peptides in inhibiting liver cancer growth in athymic mice. These finding indicates that addition of a vascular targeting sequence can enhance the biological activity of an antiangiogenic peptides molecule.
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