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

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 (Co2 +, Ni2 +, Zn2 + Cd2 + and Cu2 +) 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 Mg2 +-induced catalytic cleavage of the ribozyme. In comparison, Co2 + and Ni2 + 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-1H-1,2,3-triazole-4-carboxylic acid amide inhibited the cleavage reaction 4–5-fold more strongly.Additionally, the application of Zn2 + complexes of 1,2,3- and 1,2,4-triazole instead of catalytic Mg2 + ion, promoted the cleavage activity of the ribozyme at pH 5.5. The 1,2,3-triazole-Zn2 + complex was found to be the most effective.

Graphical abstractWe report that complexes of triazole derivatives with transition metal ions (Co2 +, Ni2 +, Zn2 +, Cd2 +, and Cu2 +) modulate the catalytic activity of antigenomic HDV ribozyme in a pH-dependent manner.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Interaction complexes of triazole-transition metals with HDV ribozyme were tested. ► Impact of complexes on the catalytic activity of ribozyme is strongly pH dependent. ► At physiological pH complexes inhibit the catalytic activity of HDV ribozyme. ► Complexes of 1,2,4-triazole derivatives with Co2 + and Ni2 + are the most active. ► At lower pH 1,2,3-triazole-Zn2 + complex promotes cleavage of HDV ribozyme.