Lanthanides nucleic acids

Lanthanides are well-known probes for calcium, although they bind to sites more strongly than Ca2+ and do not enter cells. One useful feature is that a series of probes of slightly differing radii may be used. Tbni has a radius (1.00 A) very close to that of calcium (0.99 A), and has been used successfully in many instances. The Lnm ions have also been used to probe sites on nucleic acids normally filled with essential Mg2+ ions.107,108... 

Hydrolytic catalysis by metal ions is also important in the hydrolysis of nucleic acids, especially RNA (36). Molecules of RNA that catalyze hydrolytic reactions, termed ribozymes, require divalent metal ions to effect hydrolysis efficiently. Thus, all ribozymes are metalloenzymes (6). There is speculation that ribozymes may have been the first enzymes to evolve (37), so the very first enzymes may have been metalloenzymes Recently, substitution of sulfur for the 3 -oxygen atom in a substrate of the tetrahymena ribozyme has been shown to give a 1000-fold reduction in rate of hydrolysis with Mg2+ but no attenuation of the hydrolysis rate with Mn2+ and Zn2+ (38). Because Mn2+ and Zn2+ have stronger affinities for sulfur than Mg2+ has, this feature provides strong evidence for a true catalytic role of the divalent cation in the hydrolytic mechanism, involving coordination of the metal to the 3 -oxygen atom. Other examples of metal-ion catalyzed hydrolysis of RNA involve lanthanide complexes, which are discussed in this volume. 

In principle, paramagnetic ions also may be used to induce hyperfine shifts in nucleic acids to aid detection of binding sites. Ions with high relative magnetic anisotropy and short unpaired electron relaxation times (i.e., Co Fe and trivalent lanthanide ions except for Gd ) are candidates for such studies. Indeed, Tb and Eu ions have been used as fluorescent probes of nucleic acid structures it is expected that NMR studies also would be informative. " ... 

Beeby, A., Dickins, R.S., EitzGerald, S., et al. (2000) Porphyrin sensitization of circularly polarised near-lR lanthanide luminescence enhanced emission with nucleic acid binding. Chemical Communications, 1183. 

Various metals have been complexed to oligonucleotides to produce hydrolytic or oxidative cleavage of a target nucleic acid. Lanthanide complexes covalently attached to oligonucleotides are known to cleave single-stranded... 

Structure Probes.—The introduction of fluorescing labels into nucleic acids can yield valuable structural information, and both organic compounds and metal ions [Tb (ref. 136) and Eu (ref. 137)] have been used as fluorescent probes for tRNA and other polynucleotides. The degree of secondary structure in RNA has been estimated from Raman scattering by the phosphate group vibrations. A number of n.m.r. studies have appeared, but discussion of these is more suited to a review on n.m.r. spectroscopy. Lanthanide ions have been used as contact shift reagents to probe tRNA structure. ... 

Covalent coupling of a lanthanide luminescent chelate to bioactive molecules such as peptides, proteins, or nucleic acids makes use of the chemically reactive groups of these molecules. The most common ones are aliphatic a- or s-amines. A typical example of s-amine is lysine, the pRa of which is 9.2 so that it reacts cleanly above pH 8 to yield stable... 

Modification of the C2-symmetrical ligands to allow water solubility for the assembled helicate is another landmark (Elhabiri et al., 1999 Vandev)Tver et al., 2007) since it opens the way for the binuclear complexes to be used as lanthanide luminescence probes with a variety of applications ranging from cell imaging (Biinzli et al., 2008) to nucleic acid detection (Song et al., 2008b). The chemical robustness of the helicates, both thermod)mamically and kinetically speaking, their inherent... 

R 227 C.F.G.C. Geraldes and C. Luchinat, Lanthanides as Shift and Relaxation Agents in Elucidating the Structure of Proteins and Nucleic Acids , p. 513... 

Lanthanide-Catalyzed Hydrolysis of Phosphate Esters and Nucleic Acids... 

Lanthanide chelate-dyed polystyrene particles containing carboxylic acid groups have been covalently coated with antibodies, streptavidin [95], and nucleic acids [96] for different biomolecular-binding assays. Particulate labels can be coated with antibodies and used as such, but the obvious steric and kinetic problems associated with the large molecular size can be particularly avoided by indirect detection of the bound antibodies using, e.g., biotin-streptavidin interaction [97,... 

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