Nucleotide structural parameters

The conformations of the furanose ring in 250 nucleoside and nucleotide structures were analysed by Bartenev et al. (1987). These authors made the assumption, referred to above, that intermolecular interactions have a random effect on the structure in the crystal, and that the probability JVg of a structure crystallizing in a non-ground-state conformation is the same as the probability of it arising in thermal equilibrium at ambient temperature T in solution (6). (A difficulty arises immediately with the definition of the temperature, because structural parameters for molecules in crystals are... 

Table 5.2 Nucleosides, nucleotides and oligonucleotides for which Jhh has been used as a structural parameter...

A large number of stable conformations of both natural and synthetic DNA have been observed. They may be characterized in terms of gross structural parameters such as N, the number of molecular asymmetric units in K turns of the helix h, the axial rise per residue and r, the axial rotation per residue. Both right- and left-handed helices have been observed [13, 43]. In typical cases the molecular asymmetric unit is a mononucleotide but dinucleotide asymmetric units have been found in molecules in which the chemical repeat consists of two nucleotides [11]. The nucleotide conformations can be related to the different helical parameters both in terms of the backbone and conformational angles and features such as the sugar pucker and the base-pair displacement and orientation with respect to the helix axis. 

Multiple Conformations Ensembles. When multiple conformations are present, the problem rapidly becomes underdetermined. For example, if a nucleotide can exist in two major conformational states, with x(N)P(N) and x(S)P(S) where the glycosidic torsion angles in the N and S sugar states are not equal, each conformation will have its own characteristic NOEs and coupling constants. For n bases, there are 2" conformations, and the contribution of each one to the ensemble will depend on its population. Even for a dinucleotide, there are at least 4 conformations (viz. SS, SN, NS, NN), which multiplies the number of structural parameters to be determined fourfold, plus four equilibrium constants. There are not enough independent NMR data to determine all of these parameters and the problem is underdetermined. In this situation, the best that can be hoped for is to derive a set of structures that in some way represent the ensemble of structures that is present in solution. 

Molecular mechanics and dynamics studies of metal-nucleotide and metal-DNA interactions to date have been limited almost exclusively to modeling the interactions involving platinum-based anticancer drugs. As with metal-amino-acid complexes, there have been surprisingly few molecular mechanics studies of simple metal-nucleotide complexes that provide a means of deriving reliable force field parameters. A study of bis(purine)diamine-platinum(II) complexes successfully reproduced the structures of such complexes and demonstrated how steric factors influenced the barriers to rotation about the Pt(II)-N(purine) coordinate bonds and interconversion of the head-to-head (HTH) to head-to-tail (HTT) isomers (Fig. 12.4)[2011. In the process, force field parameters for the Pt(II)/nucleotide interactions were developed. A promising new approach involving the use of ab-initio calculations to calculate force constants has been applied to the interaction between Pt(II) and adenine[202]. 

This method is especially suitable for studies with polymer nucleotide-metal ion interaction. When dissolved nucleic acids are exposed with and without metal ions to an increase of temperature structural changes, some reversible, some irreversible can be observed (27, 24, 27, 30, 39, 54—56, 75, 100, 108). The two parameters Tm (or midpoint of the transition) and a (the width of the transition) allow conclusions about conformational alterations. The application of this procedure for quantitative studies of metal complexing still needs to be elucidated. 

DNA Synthesis for Nanoconstruction Single strands of DNA, otherwise known as oligomers, are most commonly produced using a solid-support synthesis process [161, 162], This is a cyclic process where each nucleotide is sequentially coupled to form a nucleotide chain (working from the 3 end to the 5 end). The 3 end is initially covalently linked to a solid support and the nucleotide monomers are added sequentially. This is a well-established process and its key parameters and critical process steps are well documented in the literature [163,164],The DNA strands can be tailored according to the desired nanoconstruction scheme and target structure [165]. 

RJ. Unrau, D.R Bartel, RNA-Catalysed Nucleotide Synthesis , Natme, 395,260 (1998) D.H. Mathews, J. Sabina, M. Zucker, D.H. Turner, Expanded Sequence Dependence of Thermodynamic Parameters Improves Prediction of RNA Secondary Structure ,... 

The application of LSR to amino-acids has received some attention. (451-456, 498) Such studies are an essential preliminary to the use of LSR for amino-acid sequence determination in simple peptides and proteins. The latter are discussed more comprehensively in Section G. A detailed study has been made (453) of the interaction of Eu(iii), Pr(iii), Gd(iii), and La(iii) with iV-acetyl-L-3-nitrotyrosine in order to characterize the nitrotyrosine residue as a potential specific lanthanide binding site in proteins. The parameters of the dipolar interaction indicate a significant contribution from non axially symmetric terms. The conformations of the nucleotides cyclic j8-adenosine 3, 5 -phosphate (3, 5 -AMP) (457, 458) and adenosine triphosphate (ATP) (459) have been deduced using LSR. In the former case the conformation of the ribose and phosphate groups is consistent with the solid state structure. A combination of lanthanide shift and relaxation reagents was used to deduce the most favoured family of conformations for ATP in aqueous solution. One of these conformations corresponds closely to one of the crystal structure forms. 

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