Base moiety selectivity in cleavage of short oligoribonucleotides by di- and tri-nuclear Zn(II) complexes of azacrown-derived ligands

Abstract

Cleavage of 6-mer oligoribonucleotides by the dinuclear Zn²⁺ complex of 1,3-bis[(1,5,9-triazacyclododecan-3-yl)oxymethyl]benzene (L¹) and the trinuclear Zn²⁺ complex of 1,3,5-tris[(1,5,9-triazacyclododecan-3-yl)oxymethyl]benzene (L³) has been studied. The dinuclear complex cleaves at sufficiently low concentrations ([(Zn²⁺)₂L¹] ≤ 0.1 mmol L⁻¹) the ^5′NpU^3′ and ^5′UpN^3′ bonds (N = G, C, A) much more readily than the other phosphodiester bonds, but leaves the ^5′UpU^3′ site intact. The trinuclear (Zn²⁺)₃L³ complex, in turn, cleaves the ^5′UpU^3′ bond more readily than any other linkages, even faster than the ^5′NpU^3′ and ^5′UpN^3′ sites. Somewhat unexpectedly, the ^5′UpNpU^3′ site is cleaved only slowly by both the di- and tri-nuclear complex. The base-moiety selectivity remains qualitatively similar, though slightly less pronounced, when the hexanucleotides are closed to hairpin loops by three additional CG-pairs of 2′-O-methylribonucleotides. Phosphodiester bonds within a double helical stem are not cleaved, not even the ^5′UpU^3′ sites. Guanine base also becomes recognized by (Zn²⁺)₂L¹ and (Zn²⁺)₃L³, but the affinity to G is clearly lower than to U. The trinuclear cleaving agent, however, cleaves the ^5′GpG3′ bond only 35% less readily than the ^5′UpU3′ bond.