Nucleic Acid–Metal Ion Interactions

Abstract

Nucleic acids (DNA and RNA) are actually salts (or complexes) of metal ions from a chemical point of view. It is impossible to separate the behavior of DNA and RNA from their interactions with metal ions. Metal ions are usually required to promote and stabilize functionally active or native conformations of nucleic acids, as well as to mediate nucleic acid‐protein interactions. However, certain metal ions can also cause structural transformation of nucleic acids, and induce their chemical modification and cleavage. Metal‐nucleic acid interactions are involved in nucleotide biochemistry; genetic information storage and transfer, and control of gene expression, as well as in mutagenesis and carcinogenesis. However, in most cases, it is not currently clear whether the observed effects actually result from direct metal ion‐nucleic acid interaction, since other species, such as specific proteins, may be mediators between the metal ion and the nucleic acid in these processes in vivo . Interest in metal‐nucleic acid interactions is also enhanced by studies of the mechanisms of antitumor activity of certain platinum metal compounds, finding metal ions in crystal structure of natural RNA molecules, studies of the mechanism of RNA catalysis and possible involvement of metal ions in origin of life, as well as by the use of metal ions as structural probes of nucleic acids and as biotechnology tools. This article does not attempt to be comprehensive, but rather presents selected examples to illustrate key facets of metal ion‐nucleic acid interaction. The focus is on the chemical and structural properties of both nucleic acids and metal ions relevant to their interactions. Nucleic acid‐metal interactions can be either nonspecific or dependent on the chemical nature, sequence, and structure of nucleic acids. However, the specificity of these interactions is dependent on structural and chemical properties of both the nucleic acids and the metal ions. Both nucleic acids and metal ions exhibit considerable complexity in their interactions, and such interactions could affect the chemical and biochemical properties of both species.

The nonenzymatic template-directed ligation of oligonucleotides

“…At pH 7.2, catalytic activity of the divalents increased in the order: Mg<Mn<Co. The catalytic activity of the metal ions inversely correlates with pKa of metal-bound water molecules (here and after pKa w ):12(Mg)>10.7(Mn)>8.7 (Co) (Kazakov et al, 1994). Since pH of the reaction buffer was lower than these pKa w values, it indicates that the catalytic activity of the ions is proportional to concentration of the metal-bound hydroxide, which could participate in all three activation pathways mentioned above.…”

Metal‐Ion‐Dependent Folding of a Uranyl‐Specific DNAzyme: Insight into Function from Fluorescence Resonance Energy Transfer Studies

“…To address this question further, we investigated the folding of stem II–III in the presence of the Group IIA series of metal ions in a buffer with 100 m M Na + . The ionic radii for Mg 2+ , Ca 2+ , and Sr 2+ are 0.66, 0.99, and 1.12 Å, respectively 47. As shown in Figure S2 in the Supporting Information, all three metal ions promoted folding of 39E.…”

“…The ionic radii for Mg 2+ , Ca 2+ , and Sr 2+ are 0.66, 0.99, and 1.12 Å, respectively. [47] As shown in Figure S2 in the Supporting Information, all three metal ions promoted folding of 39E. The apparent binding affinity between these metal ions and 39E decreases as the ionic radius of the metal ions increases.…”

“…Because the ionic radii of Mg 2+ , Zn 2+ , U (+VI) in UO 2 2+ , and Pb 2+ are 0.66, 0.74, 0.80, and 1.20 Å, respectively, [47] one explanation for the apparently different folding behaviors of 39E in the presence of these ions is the different sizes or geometries of the metal ions that the DNAzyme interacted with; the greater size of Pb 2+ and the different, more linear-shaped UO 2 2+ ions do not induce significant folding of the 39E DNAzyme, whereas the smaller ions Mg 2+ and Zn 2+ do. To address this question further, we investigated the folding of stem II–III in the presence of the Group IIA series of metal ions in a buffer with 100 m m Na + .…”

Binding of Al(iii) to synthetic RNA and metal-mediated strand aggregation

“…Numerous studies on the effect of mono-and divalent metal ions abound in the scientific literature, and different attempts to rationalize their behaviour have been made. 1,2 Metal cations can bind to monomer units of the chain through two coordination sites: (i) the phosphate group (the main coordination site of mono-and divalent cations of Groups I and XII); [3][4][5][6] (ii) the nitrogenous bases (main site for transition divalent metal ions). [3][4][5][6][7] In addition, such ions can interact through more than one reaction site, forming chelate (phosphate-phosphate) and macrochelate (nitrogenous base-phosphate) adducts.…”