Solvent effects on dinucleotide conformation

The temperature dependence of the circular dichroism spectra of two adenylyladenosine and three adenylyluridine dinucleotides in aqueous solution have been studied. The effect of methylation of the N-6 position of the adenylyl moieties on the thermodynamic parameters of the stacking equilibrium was investigated applying a two-state model for the thermodynamic analysis of the experimental data. It is shown that the methylated compounds allow a more accurate analysis of the data and that methylation stabilizes the stacking interaction by a relative decrease of the entropy of unstacking.The rather unique vertical base-base stacking interaction exhibited by polynucleotides to form a single helix is understood to be one of the major driving forces in the formation of stable three-dimensional structures of RNA and DNA (e.g. double helices, various internal loops, hairpin loops and so forth). However, before the conformational properties of polymers can be understood in some measure, the stacking interaction must be investigated in the greatest possible detail in simple model compounds. Even if extrapolation of experimental findings in dinucleotides to properties of polynucleotides may prove to be of partial validity, one may be certain that knowledge of the differences in conformational behaviour between dinucleotides, trinucleotides and tetranucleotides will in the long run enable us to build a consistent picture of factors governing the equilibrium between helix and random coil forms in polynucleotides. For these reasons the conformational analysis of dinucleoside phosphates has received much attention during the past two decades. Most of the early papers on this subject concerned studies of the geometry and the thermodynamics of the stacking interaction by means This paper is number XV in a series from this laboratory entitled Nucleic Acid Constituents; the previous paper appeared elsewhere [C.A. G Ahhrevicrtions. CD, circular dichroism; ApU, adenylyl(3'-5')-uridine; ApA, adenylyl(3'-5')adenosine: m6ApU, N6-methyl-adenylyl(3'-5')uridine; m:ApU, N6-dimelhyl-adenosy1y1(3'5')uridine; mpApm:A, N6-dimethyl-adenylyl(3'-5')N6-dimethyl-adenosine.of optical methods viz. ultraviolet spectroscopy, optical rotatory dispersion and circular dichroism (CD) [l -51. Later, the advent of high-field Fourier-transform nuclear magnetic resonance (NMR) instrumentation allowed the complete assignment and analysis of the spectra of a wide variety of dinucleotides, providing information about the conformational changes in the dinucleotide backbone as a function of temperature [6 -101. From that time the interest for optical measurements receded to the background, presumably because of the lack of reproducibility and precision of the derived energy parameters, strikingly illustrated by the wide spread in published enthalpy values of unstacking (21 -42 kJ/mol) in ApA [ll].In previous studies [ 12 -141 we have already indicated the importance of the application of a combination of experimental techniques, i.e. C D and NMR, in the approach of ...

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“…A similar conclusion was drawn by Lowe et al [5] in the case of ApA. The 'best parameters' from Tables 2 and 3 are collected in Table 4.…”

Section: Thermodynamics Of Stackingsupporting

confidence: 77%

Circular Dichroism Studies of 6‐N‐Methylated Adenylyladenosine and Adenylyluridine and Their Parent Compounds

Olsthoorn

Haasnoot

Altona

1980

European Journal of Biochemistry

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“…It turned out that the concept of controlling the conformational distribution by the solvent works well. 55 The dinucleotide 1G in MeOH adopts mainly an open and unfolded geometry, and in H 2 O primarily a stacked conformation. Charge transfer occurs only in the stacked conformation due to the significantly larger distance between BP and the nucleobase in the unfolded geometry.…”

Section: Discussionmentioning

confidence: 99%

Conformational control of benzophenone-sensitized charge transfer in dinucleotides

Merz

Wenninger

Weinberger

et al. 2013

Phys. Chem. Chem. Phys.

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Charge transfer in DNA cannot be understood without addressing the complex conformational flexibility, which occurs on a wide range of timescales. In order to reduce this complexity four dinucleotide models 1X consisting of benzophenone linked by a phosphodiester to one of the natural nucleosides X = A, G, T, C were studied in water and methanol. The theoretical work focuses on the dynamics and electronic structure of 1G. Predominant conformations in the two solvents were obtained by molecular dynamics simulations. 1G in MeOH adopts mainly an open geometry with a distance of 12-16 Å between the two aromatic parts. In H 2 O the two parts of 1G form primarily a stacked conformation yielding a distance of 5-6 Å. The low-lying excited states were investigated by electronic structure theory in a QM/MM environment for representative snapshots of the trajectories. Photo-induced intramolecular charge transfer in the S 1 state occurs exclusively in the stacked conformation. Ultrafast transient absorption spectroscopy with 1X reveals fast charge transfer from S 1 in both solvents with varying yields. Significant charge transfer from the T 1 state is only found for the nucleobases with the lowest oxidation potential: in H 2 O, charge transfer occurs with 3.2 Â 10 9 s À1 for 1A and 6.0 Â 10 9 s À1 for 1G. The reorganization energy remains nearly unchanged going from MeOH to the more polar H 2 O. The electronic coupling is rather low even for the stacked conformation with H AB = 3 meV and explains the moderate charge transfer rates. The solvent controls the conformational distribution and therefore gates the charge transfer due to differences in distance and stacking.

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“…After this manuscript was completed three publications [27,52,53] concerned with the interpretation of CD spectra of dinucleotides have appeared. Johnson et al [52] conclude that structures other than anti-anti right-handed helices could give stable stacked molecules.…”

Section: Discussionmentioning

confidence: 99%

Oligonucleotide Conformations

Guschlbauer¹,

Frič²,

Holý³

1972

European Journal of Biochemistry

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Guanylyl‐3′‐5′‐uridine (GpU) and seventeen GpU analogues modified mostly on the uridine moiety have been investigated by circular dichroism (CD). The following conclusions can be drawn from this investigation. At room temperature and neutral pH GpU is very little, if at all stacked. A perpendicular structure with guanosine in syn and uridine with ϕCN∼+75°± 15°C stabilized by a hydrogen bond between the amino group of guanosine and the C‐4 keto group of uridine is proposed. In this structure C‐5 and C‐6 would be hidden by the guanosine base. At low temperature or low pH stacking occurs. The structure is possibly the same under these conditions and may involve guanosine in syn and uridine in anti. Substitution at C‐5 of uridine inhibits the formation of the neutral perpendicular structure. Seven C‐5 substituted GpU analogues all show CD spectra close to those of GpU at low temperature or low pH. Substitution on C‐6 of uridine destabilizes the formation of all these structures.

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Solvent effects on dinucleotide conformation

Cited by 72 publications

References 34 publications

Circular Dichroism Studies of 6‐N‐Methylated Adenylyladenosine and Adenylyluridine and Their Parent Compounds

Circular Dichroism Studies of 6‐N‐Methylated Adenylyladenosine and Adenylyluridine and Their Parent Compounds

Conformational control of benzophenone-sensitized charge transfer in dinucleotides

Oligonucleotide Conformations

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