Effect of the ribose versus 2′-deoxyribose residue on the metal ion-binding properties of purine nucleotides

Skilandat

Metal Ions in Life Sciences

et al. 2012

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Cadmium(II), commonly classified as a relatively soft metal ion, prefers indeed aromaticnitrogen sites (e.g., N7 of purines) over oxygen sites (like sugar-hydroxyl groups). However, matters are not that simple, though it is true that the affinity of Cd(2+) towards ribose-hydroxyl groups is very small; yet, a correct orientation brought about by a suitable primary binding site and a reduced solvent polarity, as it is expected to occur in a folded nucleic acid, may facilitate metal ion-hydroxyl group binding very effectively. Cd(2+) prefers the guanine(N7) over the adenine(N7), mainly because of the steric hindrance of the (C6)NH(2) group in the adenine residue. This Cd(2+)-(N7) interaction in a guanine moiety leads to a significant acidification of the (N1)H meaning that the deprotonation reaction occurs now in the physiological pH range. N3 of the cytosine residue, together with the neighboring (C2)O, is also a remarkable Cd(2+) binding site, though replacement of (C2)O by (C2)S enhances the affinity towards Cd(2+) dramatically, giving in addition rise to the deprotonation of the (C4)NH(2) group. The phosphodiester bridge is only a weak binding site but the affinity increases further from the mono-to the di-and the triphosphate. The same also holds for the corresponding nucleotides. Complex stability of the pyrimidine-nucleotides is solely determined by the coordination tendency of the phosphate group(s), whereas in the case of purine-nucleotides macrochelate formation takes place by the interaction of the phosphate-coordinated Cd(2+) with N7. The extents of the formation degrees of these chelates are summarized and the effect of a non-bridging sulfur atom in a thiophosphate group (versus a normal phosphate group) is considered. Mixed ligand complexes containing a nucleotide and a further mono-or bidentate ligand are covered and it is concluded that in these species N7 is released from the coordination sphere of Cd(2+). In the case that the other ligand contains an aromatic residue (e.g., 2,2'-bipyridine or the indole ring of tryptophanate) intramolecular stack formation takes place. With buffers like Tris or Bistris mixed ligand complexes are formed. Cd(2+) coordination to dinucleotides and to dinucleoside monophosphates provides some insights regarding the interaction between Cd(2+) and nucleic acids. Cd(2+) binding to oligonucleotides follows the principles of coordination to its units. The available crystal studies reveal that N7 of purines is the prominent binding site followed by phosphate oxygens and other heteroatoms in nucleic acids. Due to its high thiophilicity, Cd(2+) is regularly used in so-called thiorescue experiments, which lead to the identification of a direct involvement of divalent metal ions in ribozyme catalysis.

“…insert Tables 10 and 11 [121]. In the case of ATP 4-/dATP 4-the 2'-deoxy complexes are somewhat more stable and show also a slightly enhanced tendency for macrochelate formation.…”

Section: Complexes Of Nucleoside 5'-di-and Triphosphatesmentioning

confidence: 81%

“…The stability constants (eq. 2), which correspond to these pK a values [115,117], are listed in columns 3 to 5 of Table 7 (upper part) [121,122] for several M(R-MP), M(R-DP) -, and M(R-TP) 2-complexes.…”

Section: Complexes Of Cadmium(ii) With Phosphatesmentioning

confidence: 99%

Complex Formation of Cadmium with Sugar Residues, Nucleobases, Phosphates, Nucleotides, and Nucleic Acids

Skilandat

Metal Ions in Life Sciences

et al. 2012

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“…1A). [4,[24][25][26] Along the same lines, also in the case of longer nucleic acids, the most prominent sites for metal ions are the two non-bridging oxygen atoms of the negatively charged phosphatesugar backbone (Fig. 1A).…”

Section: Metal Ion Binding In Natural Systemsmentioning

confidence: 82%

Exploring Metal Ion Coordination to Nucleic Acids by NMR

Johannsen¹,

Korth²,

Schnabl³

et al. 2009

Chimia

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Metal ions play a crucial role in charge compensation, folding and stabilization of tertiary structures of large nucleic acids. In addition, they may be directly involved in the catalytic mechanism of ribozymes. Most metal ions applied in the context of nucleic acids in vivo and in vitro bind in a kinetically labile fashion. Hence, the detection of metal ion binding sites, not to mention the elucidation of the specific coordination sphere, still poses largely unresolved problems. Here we describe the different strategies applied and the progress made over the last years to characterize metal ion coordination to large nucleic acids by NMR. Metal ions play a crucial role in charge compensation, folding and stabilization of tertiary structures of large nucleic acids. In addition, they may be directly involved in the catalytic mechanism of ribozymes. Most metal ions applied in the context of nucleic acids in vivo and in vitro bind in a kinetically labile fashion. Hence, the detection of metal ion binding sites, not to mention the elucidation of the specific coordination sphere, still poses largely unresolved problems. Here we describe the different strategies applied and the progress made over the last years to characterize metal ion coordination to large nucleic acids by NMR.

“…a Levenberg-Marquardt [7,196,286,287] or a Newton-Gauss [288] algorithm and binding constants can be deduced. This has been widely used for small complexes [25,27,40,86,[289][290][291], as well as for more complicated nucleic acids [7].…”

Section: Calculating Site-specific Intrinsic Binding Affinities From mentioning

confidence: 99%

“…Hard metal ions find suitable binding sites in the negatively charged non-bridging phosphate oxygens of the backbone and also in the exocyclic nucleobase oxygens [34], while the endocyclic nitrogens of the nucleobases are a preferred target of softer metal ions ( Figure 1) [8,[34][35][36][37][38]. Also available are the bridging phosphate oxygens and the 2'-hydroxyl groups of sugar moieties [39,40]. The exocyclic amino groups of the nucleobases are usually not suitable liganding sites because of the delocalization of the lone pair into the aromatic ring.…”

Section: Ligating Sites For Metal Ions In Nucleic Acidsmentioning

confidence: 99%

Characterization of Metal Ion-Nucleic Acid Interactions in Solution

Pechlaner

Metal Ions in Life Sciences

2011

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Metal ions are inextricably involved with nucleic acids due to their polyanionic nature. In order to understand the structure and function of RNAs and DNAs, one needs to have detailed pictures on the structural, thermodynamic, and kinetic properties of metal ion interactions with these biomacromolecules. In this review we first compile the physicochemical properties of metal ions found and used in combination with nucleic acids in solution. The main part then describes the various methods developed over the past decades to investigate metal ion binding by nucleic acids in solution. This includes for example hydrolytic and radical cleavage experiments, mutational approaches, as well as kinetic isotope effects. In addition, spectroscopic techniques like EPR, lanthanide(III) luminescence, IR and Raman as well as various NMR methods are summarized. Aside from gaining knowledge about the thermodynamic properties on the metal ion-nucleic acid interactions, especially NMR can be used to extract information on the kinetics of ligand exchange rates of the metal ions applied. The final section deals with the influence of anions, buffers, and the solvent permittivity on the binding equilibria between metal ions and nucleic acids. Little is known on some of these aspects, but it is clear that these three factors have a large influence on the interaction between metal ions and nucleic acids.