Regulation of the antigenomic delta ribozyme catalytic activity by complexes of triazole derivatives with transition metal ions in a pH-dependent manner

Abstract

Abstract The effect of several triazole compounds (1,2,4-triazole and its 3-ethoxycarbonyl derivative as well as 1,2,3-triazole, its 4-[ N -methyl(2,2,2-trifluoroacetamide)] derivative and two 1,2,3-triazole ribonucleosides) and their complexes with transition metal ions (Co 2 + , Ni 2 + , Zn 2 + Cd 2 + and Cu 2 + ) on the catalytic activity of antigenomic HDV ribozyme was tested at different pH values. Investigated at pH 7.5, 1,2,3- and 1,2,4-triazole derivatives only slightly inhibited Mg 2 + -induced catalytic cleavage of the ribozyme. In comparison, Co 2 + and Ni 2 + complexes of 1,2,3-triazole and their derivatives, namely, N -(1,2,3-triazol-4-yl)methyl-2,2,2-trifluoroacetamide and 1-β- d -ribofuranosyl-1 H -1,2,3-triazole-4-carboxylic acid amide inhibited the cleavage reaction 4–5-fold more strongly. Additionally, the application of Zn 2 + complexes of 1,2,3- and 1,2,4-triazole instead of catalytic Mg 2 + ion, promoted the cleavage activity of the ribozyme at pH 5.5. The 1,2,3-triazole-Zn 2 + complex was found to be the most effective.