Natural nucleic acids

There are large numbers of biological studies pertaining to the action of DNA inside and outside the cell, which is a broad and different subject area. Hence we suggest that the readers resort to the books indicated [343-345]. 

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Since these basic facts became known, a tremendous amount of research has been done on the structures and behaviors of these important substances. There has also been much research on the synthesis and study of other chain polyelectrolytes, containing hydrogen-bond-forming radicals (R) more-or-less like those in the natural nucleic acids. The primary aim of this research is, of course, to relate the behavior of the synthetic materials to the behavior of the natural ones. Okubo and Ise here present an excellent discussion on this research. 

Note 3 Polyelectrolytes can be either synthetic or natural. Nucleic acids, proteins, teichoic acids, some polypeptides, and some polysaccharides are examples of natural polyelectrolytes. 

Guanine is the most easily oxidizable natural nucleic acid base [8] and many oxidants can selectively oxidize guanine in DNA [95]. Here, we focus on the site-selective oxidation of guanine by the carbonate radical anion, COs , one of the important emerging free radicals in biological systems [96]. The mechanism of COs generation in vivo can involve one-electron oxidation of HCOs at the active site of copper-zinc superoxide dismutase [97, 98], and homolysis of the nitrosoperoxycarbonate anion (0N00C02 ) formed by the reaction of peroxynitrite with carbon dioxide [99-102]. 

Relatively few simple pyrimidine monomers have been incorporated into heterocyclic polymers (70MI11100). By far the greatest efforts with this ring system have involved polymerizable derivatives of nucleic acid bases and related compounds (81MH1102). The majority of this work has involved the synthesis and free radical polymerization of suitable vinyl- and acrylic-functional monomers, e.g. (134)-(136), although epoxy and other derivatives have also been studied. A number of the polymers exhibit base-paired complex formation with natural nucleic acid polymers or synthetic analogues, have found use in... 

The target for microarray experiments can be of different nature. Nucleic acids are more commonly used nowdays. Diverse techniques can be used for target labeling. Selection in each case depends upon the molecular and biological nature of the target. Binding of the labeled target nucleic acids to... 

Bonen L, Cunningham RS, Gray MW, Doolittle WF (1977) Wheat embryo mitochondrial 18S ribosomal RNA Evidence for its prokaryotic nature. Nucleic Acids Res 4 663-667 Buchner P (1965) Endosymbiosis of animals with plant microorganisms. Interscience, New York... 

Moreover, natural nucleic acids give rise to two well-separated oxidation peaks in differential pulse voltammograms, which can be used to probe individual adenine-thymine (AT) and guanine-cytosine (GC) pairs in double helical DNA during its conformational changes [38]. Differences in signals obtained at carbon electrodes were observed according to whether, or not, the DNA was denatured [39]. 

The difficulties encountered in the untemplated synthesis of natural nucleic acids is one factor that has prompted many researchers to propose alternatives to RNA as the initial genetic material. For example, a derivative of 3 -aminoguanosine can form untemplated chains of up to 20 bases in length.25 In addition, both cyclic and acyclic nucleotide bisphosphate derivatives polymerize without the aid of a template to form nucleic acids with pyrophosphate linkages between the monomers, rather than the more natural phosphodiester linkages.26-29... 

Because of the complex behaviour to be expected for natural nucleic acids, it is only natural that considerable effort has been devoted to studies of the electrochemical properties of their monomeric units, and defined analogues of these, as well as of synthetic oligo- and polynucleotides. A variety of techniques has been applied for this purpose, and some of the details and findings are covered in several reviews 19 24). Most investigations have dealt with electroreduction processes 15 20,24,25). Only relatively recently has attention been directed to possible electrooxidation of nucleic acids and their constituents with the aid of the graphite electrode which, in comparison with the mercury electrode, possesses a much greater accessible range of positive potentials 26 29). 

Current chemical literature contains numerous examples of attempts to synthesize compounds corresponding to biocatalysts, affinity receptors, or natural nucleic acids, together with examples of their analytical applications. 

Monomers (VII) and (VIII) have been studied the most extensively. The original work on polymerizing (VII) lead to an intractable. Insoluble, cyclopolymerlzed polymer (40) but subsequent work lead to linear, water soluble polymers (jH, ). Monomer (Vlll) readily polymerizes under free radical conditions to form linear, water soluble polymers ( J,, ). The polymers of (Vll) and (Vlll) form complexes with each other in a manner similar to the natural nucleic acids (.25,2 and they do show antitumor activity against murine leukemia virus (45,46). 

Figure 16.2. Chemical formulas of the monomer units (in their pairing conformation) of the natural nucleic acids DNA and RNA, as well as of the nucleic-acid alternatives that have been investigated experimentally.

Many anti-viral compounds are analogues of the natural nucleic acid nucleosides such as adenosine 225. This example 226, known as (5, 5 )-iso-ddA (dda stands for di-deoxy-adenosine), has a severely modified sugar 227 but the purine, adenine 228, is unaltered. The purine is attached to C-2 instead of C-1 making the molecule more stable and two of the OH groups have been removed. Coupling adenine to the modified sugar 227 needs a Mitsunobu process.42... 

The complementary reaction of nucleic acids has one of the strongest binding affinities found in nature. Nucleic acid probe assays have been developed extensively in research on genetics, forensics, microbiology, and oncology (242,243). Applications of nucleic acid probe assays for pharmaceutical analysis are still limited at this time and are beyond the scope of this chapter. 

Non-phosphate three-atom 2 -5 -linked oligonucleotides constitute a significantly different modification, although at the first glance they resemble 2 -5 -phosphate-linked ODNs and ORNs Like natural nucleic acids, they exhibit six connecting atoms in their SRU. Molec-... 

Combinatorial bioengineering, in which targeting molecules are selected from a random molecular library, has been used to prepare functional polymers that have a molecular recognition and catalysis capability, and biodevice polymers based on these functionalities. Although the polymer content is limited to natural nucleic acids and amino acids, this has been extended to nonnatural compounds. The possibility of developing new functional polymers using combinatorial bioengineering is discussed. 

The type and number of the functional groups of a natural nucleic acid or amino acid are limited. If a nonnatural nucleic or amino acid can be applied to in vitro selection, then the scope of the functional oligomers or polymers will be extended (55, 54). 

These are phosphoric acid esters of nucleosides in which there is a phosphate group at position C-5. Nucleotides with phosphorylation at other positions do exist, but they are not components of natural nucleic acids. 

This article is devoted to a comprehensive review of theoretical and experimental results on excited state properties (electronic transitions, excited state geometries, charges, interaction etc.) of the natural nucleic acid bases and base pairs. It is well known that there are three important components of DNA. 

The predominant feature of nucleic acids in aqueous solution is the ionic nature of their phosphate groups which makes these molecules ideal candidates for separation by ion-exchange chromatography. Reversed phase separations may also be carried out by utilising the weak hydrophobic nature of the nucleic acid bases. Natural nucleic acids occur in many different size classes and group separations (e.g. between ribosomal RNA and transfer RNA) by size exclusion can also be effective. The relative merits of these methods are described in the following sections. 

Aptamer is a globular-shaped oligonucleotide that is identified by the systematic evolution of ligands by exponential enrichment (SELEX) process. It has the similar composition as natural nucleic acid, but the nucleotides of aptamer have 2 -modified sugars to enhance the nuclease resistance [122]. Since its discovery in 1990, aptamer has become a valuable research tool. Aptamers can specifically bind to target protein with high affinity, therefore it can be utilized in the targeted delivery of siRNA [37,123]. For example, prostate-specific membrane... 

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