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

: Laine M, Ketomaki K, Poijarvi-Virta P, Lonnberg H

Publisher: ROYAL SOC CHEMISTRY

: 2009

ORGANIC & BIOMOLECULAR CHEMISTRY

: ORG BIOMOL CHEM

: 7

: 13

: 2780

: 2787

: 8

: 1477-0520

DOI: https://doi.org/10.1039/b904828f

Cleavage of 6-mer oligoribonucleotides by the dinuclear Zn(2+) complex of 1,3-bis[(1,5,9-triazacyclododecan-3-yl)oxymethyl]benzene (L(1)) and the trinuclear Zn(2+) complex of 1,3,5-tris[(1,5,9-triazacyclododecan-3-yl)oxymethyl]benzene (L(3)) has been studied. The dinuclear complex cleaves at sufficiently low concentrations ([(Zn(2+))(2)L(1)] <= 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 (Zn(2+))(3)L(3) 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 (Zn(2+))(2)L(1) and (Zn(2+))(3)L(3), but the affinity to G is clearly lower than to U. The trinuclear cleaving agent, however, cleaves the (5')GpG(3') bond only 35% less readily than the (5')UpU(3') bond.

Chemical sciences