Nucleic acid stacking

The probability of finding a nucleic acid unit in the certain conformation according to our results is never equal to the unit. It agrees with the idea that NAs are not static but fluctuating, breathing , objects [23]. For example, in RNA molecule with 10 base pairs at the room temperature about 510 base pairs do not take part in the stacking and are not connected with H -bonds [2]. 

A hypochromicity was observed between THPVP and APVP (or TPVP). Since theophylline is not a nucleic acid base and does not form hydrogen-bonding, these observations indicate that stacking-type hydrophobic forces are important. 

Hardman SJO, Thompson KC (2006) Influence of base stacking and hydrogen bonding on the fluorescence of 2-aminopurine and pyrrolocytosine in nucleic acids. Biochem 45 9145-9155... 

Fig. 10 Charge transport is observed in a variety of nucleic acid assemblies over a wide distance regime (3.4-200 A). Shown are examples of nucleic acid structures through which charge transport has been examined a B-form DNA b DNA-RNA hybrids c cross-over junctions and d nucleosome core particles. In all assemblies, the charge transport chemistry is extremely sensitive to the structure of the -stacked nucleic acid bases...

We have now adjusted our molecular systems to provide a model in which both forces can operate simultaneously. The U-shaped relationship that exists between the imide function and amides of aryl amines creates a hydrogen bonding edge and a planar stacking surface that converge from perpendicular directions as in 44 to provide a microenvironment complementary to nucleic acid components. A large number of aromatic rings can be functionalized with this simple scaffold, and spacers (R) can also be incorporated. The imide function is a mimic of the thymine residues. 

It is assumed that tholins also played an important role in the PAH world hypothesis. The PAH world could have existed as a pre-RNA world on the primeval Earth. It is suggested that PAHs can undergo stacking, thus forming structures to which nucleobases are chemically bound (to OH functions which are formed by photochemical derivatisation of the PAHs). The PAH stacks replace the more complex phosphate-D-ribose-phosphate chains in the nucleic acids (Ehrenfreund et al., 2006). 

Ethidium is a model compound for these studies. In human pharmacology, two classes of natural products (actinomyces, anthracyclines) provide prototypic molecules as DNA intercalating agents. (Planar molecules tend to insert well into the stacked nucleic acids, which accounts for the carcinogenic potential of polyaromatic hydrocarbons see figure 7.5.)... 

Figure 7.5 Intercalation of carcinogens into the stacked bases of nucleic acids. Both carcinogens and certain anti-neoplastic agents share a common mechanism of action. They have the capacity to insert themselves into the nucleic acid structure, causing geometrical distortions that preclnde the ability of the nucleic acid to complete its function in the processes of transcription and translation. Flat aromatic molecules have the ability to intercalate between the stacked bases.

The fluorescence of 2AP is strongly quenched by nucleic acid bases [17, 18, 24-29]. Time-correlated single-photon counting studies have shown that the interactions of 2AP with different nucleic acid bases significantly decrease the 2AP fluorescence hfetime [17, 24-29]. While the fluorescence lifetime of free 2AP in aqueous solution is about 10 ns, in double-stranded DNA the 2AP hfetimes are reduced to 30-50 ps. This effect has been used extensively to study the dynamics of mismatched base pairs [19, 21, 25, 30], local changes in dynamics of DNA molecules produced by their binding to the active sites of polymerases [26, 31-33], stacking interactions at abasic... 

The purine and pyrimidine bases are hydrophobic and relatively insoluble in water at the near-neutral pH of the cell. At acidic or alkaline pH the bases become charged and their solubility in water increases. Hydrophobic stacking interactions in which two or more bases are positioned with the planes of their rings parallel (like a stack of coins) are one of two important modes of interaction between bases in nucleic acids. The stacking also involves a combination of van der Waals and dipole-dipole interactions between the bases. Base stacking helps to minimize contact of the bases with water, and base-stacking interactions are very important in stabilizing the three-dimensional structure of nucleic acids, as described later. 

The close interaction between stacked bases in a nucleic acid has the effect of decreasing its absorption of UV light relative to that of a solution with the same concentration of free nucleotides, and the absorption is decreased further when two complementary nucleic acids strands are paired. This is called the hypochromic effect. Denaturation of a double-stranded nucleic acid produces the opposite result an increase in absorption... 

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