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The authors describe the discovery of synthetic human angiogenic antagonists; they did so, by inferring the antisense RNA sequence codes matching to the to the receptor-binding site (RBS) of angiogenin in either 5’→3 (chANG) or 3’→5’ (chGNA) direction. These two peptides bind to angiogenin with good specificity and with a Kd ≈ 44 nM, and in the process disrupt the interaction of angiogenin with actin, which is considered the angiogenin-binding protein on the surface of endothelial cells.These peptides block the neovascularization promoted by angiogenin in the chick chorioallantoic membrane assay (CCMA). The antagonistic activity of these peptides is angiogenin-specific, and the peptides do not seem to have an effect on embryonic angiogenesis or blood vessels already present. These peptides (chANG and chGNA) also block the angiogenesis created by the angiogenin-secreting PC 3 human prostate adenocarcinoma cells.
In conclusion, neutralization of the extracellular angiogenins secreted by PC 3 cells is achieved by the inhibition of the tumor-induced angiogenesis (peptide mediated) Therefore, chANG and chGNA synthetic peptides show potential to be effective in the treatment of angiogenin secreting human tumors.
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