Polynucleotide interactions with ions

Interactions with ions. Because each linking phospho group carries a negative charge (two charges per base pair, Fig. 5-2) the behavior of polynucleotides is strongly affected by cations of all kinds. The predominant small counterions within cells are K+ and... 

Polymetaphosphate 3 Polymorphonuclear leukocytes 26 Polynucleotide(s) 199s, 226-228. See also Nucleic acids, RNA, DNA hybridization 255 hydrazine reactions 254 interactions with ions 218 melting of 255 probes 255... 

In the following chapters the complex reaction of metals with macromolecules is discussed separately for each metal ion. To conclude this series an attempt will be made to correlate metal-polynucleotide interactions with biochemical pathways. 

Figure 27-13 Proposed mechanism and transition state structure for the synthetic nucleotidyltransfer activity of DNA polymerase 3 (and other DNA polymerases). The chain-terminating inhibitor dideoxy CTP is reacting with the 3 -OH group of a growing polynucleotide primer chain. This -OH group (as -0 ) makes an in-line nucleophilic attack on Pa of the dideoxy-CTP. Notice the two metal ions, which interact with the phospho groups and which are held by three aspartate side chains. Two of the latter, Asp 190 and Asp 256, are present in similar positions in all of the polymerases. The active centers for the hydrolytic 3 -5 and 5 -3 exonuclease activities of some of the polymerases also appear to involve two-metal catalysis and in-line displacement. See Sawaya et al.27i...

The reactivity of metal ions is not always the same with DNA and RNA. One reaction that is exclusive to RNA is depolymerization of the polynucleotide structure by the cleavage of the phosphodiester bonds. This depolymerization reaction, as with other RNA hydrolyses, can be induced by metal hydroxides, Zn being one of the most effective. A simple mechanism is that the Zn" chelates to the phosphate group and the 2 -hydroxyl group of ribose (the 2 -group is absent in DNA). Electron withdrawal by the Zn ion then weakens the phosphodiester linkage. Such a mechanism, however, does not take into account the observed influence of the nature of the adjacent base and the formation of metal-dependent products. Pb is also an effective catalyst in site-specific depolymerization of tRNA. In this case the metal has been shown to bind to the bases with only weak interactions with phosphate groups. The catalytic action has been interpreted in terms of nucleophilic attack by a metal-bonded hydroxide ion.134 This may have implications for the mechanisms of other metal ions active in this reaction. 

Why would people be interested in metal-nucleic acid interactions Perhaps because life as we know it is dependent on these interactions. Nucleic acids (DNA and RNA) are actually salts (or complexes) of metal ions from a chemical point of view. Therefore, it is difficult, if not impossible, to separate the behavior of DNA and RNA from their interactions with metal ions. We must also take into account specifically bound water molecules since they frequently mediate interactions between polynucleotides and metal ions. ... 

Large molecules, such as proteins and polynucleotides, have many charged groups that interact with an ion-exchange sorbent at many sites. Multiple-site... 

Zundel We did not examine the influence of transition metal ions on 23 S RNA or on other polynucleotides. However, we compared the interaction of Mg + and Mn + with water in poly-electrolytes. Almost no difference was observed between the interaction effects caused by these ions. Cu and Zn + ions show, however, much stronger interaction with water molecules as one should expect in the case of pure electrostatic interaction. With Cu + and Zn + ions the d-holes in the shell of these ions are of great importance for the interaction with water. For details see Reference 48. 

Scope of data. This chapter covers metal ion interactions with DNA, RNA and polynucleotides. A few related data involving oligonucleotides are included when necessary and appropriate. Oligomers when crystallized for X-ray analysis resemble polymers and are treated as such. The subject matter is limited to direct effects of metal binding, e.g. metal association constants and binding characteristics, metal binding effects on conformation, and metal-catalyzed depolymerization. There are of course many other phenomena that could be included, but are deemed unsuitable for tabulation. The effects of metal binding to DNA and RNA that involve interaction with proteins are covered only when the primary effect is on the nucleic acid moiety. 

One of the most important aspects of the interaction between metals and polynucleotides is that which leads to compactness of structure in the polynucleotides. As polyions, they exhibit structures in solution which are strongly dependent on the concentration and valence of the cations (typically, the compact native structures are favoured by high salt concentrations and particularly by bivalent ions), but even with the transfer RNAs (among the most widely studied nucleic acids and despite analysis of the X-ray structures) the role and location of bound bivalent cations are uncertain. Leroy et al. have used various physical techniques to explore the structure of the central region in a couple of tRNAs from E. coli and thereby obtain evidence on the binding of Mn + and other metal ions. Their interpretation is that simple manganese-phosphate binding is supplemented by electrostatic interaction with distant phosphates. 

G. L. Eichhom and Y. A. Shin, Interaction of metal ions with polynucleotides and related compounds. 

Mg2+. They are attracted to the negative charges on the polynucleotide backbone and, although they remain mobile, they tend to occupy a restricted volume.175 177 Some may bind in well-defined locations as in Fig. 5-8. Because of the presence of these positive ions the interactions of nucleic acids with cationic groups of proteins are strongly affected by the salt concentration. 

One may draw an analogy between nucleic acids and helicates, with on one side the polynucleotide strands and their interaction through hydrogen bonding and on the other side the oligobipyridine strands and their binding together via metal ion coordination. 

In addition to the reaction of mercaptopropionic acid, mixed anhydrides were also formed and identified starting from leucine and phenylalanine in the presence of Ca2+ ions, showing that RNAs can replace protein aminoa-cyl fRNA synthetase catalysts for amino acid activation. The formation of a detectable amount of aminoacyl S -phosphalc polynucleotide seems to be in contradiction with the instability predicted for aminoacyl adenylates (Table 1), however it can be explained by the low pH value increasing their stability and the fact that the selected RNA structures are likely to stabilize the mixed anhydride moiety of the covalent conjugate by favorable intramolecular interactions induced by folding. 

Interactions of Transition Metal Ions with Polynucleotides. 55... 

In the previous chapters the reactivity of metal ions with the monomer units of nucleic acids has been discussed. This section will deal with the binding of transition metals to the polynucleotides. There are also three types of complexes to be expected the metal-ring, the intermediate and the metal chain complex. The effect of the ribose or deoxyribose residue on the stability constants can be neglected since the reactivity of these sugars with cations is extremely low. However, as it will be seen later, the hydrolysis of polyribonucleotides is markedly facilitated by interaction of metal ions with the 2 —OH groups of the ribose. 

Butzow, J. J., and G. L. Eichhorn Interactions of metal ions with polynucleotides and related compounds. IV Degradation of polyribonucleotides by zinc and other divalent metal ions. Biopolymers 3, 97 (1965). 

---