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

• Published in: Inorganic chemistry communications 2012-06, Vol.20, p.330-333
• Main Authors: Zeidler, Joanna, Nijakowska, Danuta, Wrzesinski, Jan
• Format: Article
• Language: English
• Subjects: HDV ribozyme; pH dependence; Triazole derivatives–metal ion complexes
• ISSN: 1387-7003; 1879-0259
• DOI: 10.1016/j.inoche.2012.03.044

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. We 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. [Display omitted] ► 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.