Amino and carboxy functionalized modified nucleosides: A potential class of inhibitors for angiogenin

• Amino and carboxy functionalized nucleosides.
• Competitive inhibition of the ribonucleolytic activity of angiogenin.
• Fluorescence based enzyme kinetics.
• Inhibition of angiogenin induced angiogenesis.
• Better activity of the nucleosidic molecules compared with phosphate analogues.

The 3′-amino and carboxy functionalize thymidines execute their ribonucleolytic inhibition activity for angiogenin. These modified nucleosidic molecules inhibit the ribonucleolytic activity of angiogenin in a competitive manner like the other conventional nucleotidic inhibitors, which have been confirmed from kinetic experiments. The improved inhibition constant (Ki) values 427 ± 7, 775 ± 6 μM clearly indicate modified nucleosides are an obvious option for the designing of inhibitors of angiogenesis process. The chorioallantoic membrane (CAM) assay qualitatively suggests that amino functionalized nucleosides have an effective potency to inhibited angiogenin-induced angiogenesis. Docking studies further demonstrate the interaction of their polar amino group with the P1 site residues of angiogenin, i.e., His-13 and His-114 residues.

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