Lanthanide nucleotide complexes

Nucleotides in the form of metal ion complexes are involved in a variety of enzymatic reactions either as substrates or as cofactors. These may also be viewed as monomers of DNA and RNA. Lanthanide complexes of nucleotides have been extensively studied because (i) the conformation of nucleotides in solution can be elucidated from lanthanide induced NMR chemical shifts and line-broadenings [40] and (ii) lanthanide nucleotide complexes may act as competitive inhibitors in enzymatic reactions [88] and hence can be used as paramagnetic probes in the mapping of their binding site on the enzyme [89]. 

Complex formation constants for lanthanide nucleotide complexes are given in Table 11.12. 

Dissociation constants (at 25-29°C) of lanthanide-nucleotide complexes at acidic pH... 

Lanthanide complexes, [Ln(dpa)3]3+ (Ln = Eu3 + or Tb3 + ), were also applied to the stereoselective quenching reaction by cobalt(III) nucleotide complexes, shown in Scheme 31 [75]. 

To date, D coefficients of carbohydrates established with the PFGSE approactf - " have been undertaken to (1) validate the theoretical self-diffusion coefficients calculated from MD trajectories, (2) demonstrate the complexation of lanthanide cations by sugars,(3) probe the geometry of a molecular capsule formed by electrostatic interactions between oppositely charged P-cyclodextrins, (4) study the influence of concentration and temperature dependence on the hydrodynamic properties of disaccharides, and (5) discriminate between extended and folded conformations of nucleotide-sugars. ... 

The angular and distance information provided by the lanthanide induced shift has found widespread application from the determination of solution structures of Ln chelates [18,19] to gaining structural information on proteins, nucleotides and amino acids [19], More recently anion binding to coordinatively unsaturated lanthanide complexes has been effectively signalled as the observed lanthanide induced shift has been directly correlated to the nature of the donor atom in the axial position [8,20,21], It is the polarisability of the axial donor that ranks the second order crystal field coefficient, B02, and hence determines the magnitude of the observed shift. Values of the mean shift of the four most-shifted axial protons of the 12-Nq ring for [Yb.la]3+ are collated in Table 2. 

At pH values above 7.0 the nucleotides are fully ionized and complex formation with lanthanides is more favourable. At pH 5.6 a dissociation constant of the order of 1 mM is estimated for Tb3+ complexes of nucleotide monophosphates from fluorescence measurements [93], At pH 7.0 Eu3+-ADP complex gave a value 10-7 M for Kd [96]. The dissociation constants of Ln-ATP complexes obtained by Morrison and Cleland [97] are given in Table 11.13. 

The use of paramagnetic ions to examine the binding sites and solution conformations of nucleosides and nucleotides is becoming very widespread. Studies that describe the complexing of a variety of nucleosides and nucleotides with paramagnetic ions involve the use of Mn(ii), (749-751) Cu(ii), (750, 752-754) and lanthanide ions. (755) Mn " ions appear to bind to multiple sites on purine and pyrimidine nucleosides (749) whereas the phosphate group is the primary binding site on monophosphate nucleotides. (750) relaxation studies indicate that Cu " ions bind to N-3 of 5 -cytidine monophosphate (5 -CMP). In contrast to cytidine [59], adenosine [60] appears to have... 

The conformations of nucleotides have been probed by lanthanides [73]. Furthermore, adenosine triphosphate (ATP)-lanthanide complexes are strong enough to carry the metal on to enzymes. Thus, Gd " competitively inhibits Mg -(yeast)-phosphoglycerate kinase (mol. wt. 47000) and selectively broadens histidine H resonances [74]. 

Binding sites for Ca " and ATP have been explored by the use of metal probes and nucleotide analogues. The Mn ion substitutes for Mg but also binds at the Ca " sites. Such complications have led to the use of lanthanides as probes for the Ca sites. Thus Gd " and Tb " compete with Ca for the high affinity site. Luminescence studies with laser-excited Tb " at the Ca sites show that two water molecules are present in the first coordination shell. Earlier work with Gd shows that the Ca sites are a maximum of 16.1 A apart, and that both sites involve a low level of hydration, consistent with a hydrophobic site. Gd has also been used as an ESR probe, and, under certain conditions, evidence has been produced for two forms of an E-Gd complex, in accord with current mechanistic views. 

Complexes of Lanthanide Ions with Amino Acids, Nucleotides, and Other Ligands of Biological Interest in Solution... 

Complex formation between lanthanides and nucleotides has been studied at relatively low pH (ca. 2) by NMR. A summary of dissociation constants is given in table 39.7. Barry et al. (1971) have shown that the phosphate in nucleotide monophosphates acts as a bidentate ligand. In the ATP complex the lanthanide ion interacts with the terminal and y phosphates, which act probably as a... 

In studies on nucleotides, Williams group has employed edta complexes of lanthanide ions (La +, Pr +, Eu +, and Gd +) to probe the conformations of adenosine and cytidine 5 -phosphates at pH 7.5. The conformation of cytidine 5 -phosphate at pH 2.0 was also investigated using lanthanide ions, and relaxation studies with Gd + cations confirmed the findings derived from the shift data. ... 

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