Polynucleotides, natural

Nucleic Acid. A nucleic acid is a natural polynucleotide. It is a sugar-phosphate chain with purine and pyrimidine bases attached to it, as shown in Chart 10. If the sugar is deoxyribose and the pyrimidine bases are cytosine and thymine, the nucleic acid is deoxyribonucleic acid, DNA if the sugar is ribose, and the pyrimidine bases are (mostly) cytosine and uracil, the nucleic acid is ribonucleic acid, RNA. The sequence of bases may appear arbitrary and random, but it constitutes a meaningful code (see Code Word). In double-stranded nucleic acids,... 

The data available from studies of the action of nuclease on synthetic substrates, oligonucleotides, and natural polynucleotides are consistent with the following generalizations and simplifications. It appears that... 

Especially attractive was the possibility to connect nucleosides, as has been realized, for instance, with the hexathymidine 141 and with the elongated and alternating strands 142 and 143. These compounds represent artificial oligonucleosides, which may interact with natural polynucleotides or nucleic acids. On treatment with Cu(i), 142 and 143 gave the double-helical complexes 144 and 145, respectively, inside-out analogues of double-stranded nucleic acids, which may be termed deoxy-... 

While the complementary double helical structure explained how particular sequences of bases could be used to store a genetic instruction it was not immediately clear how replication occurred or, indeed, how these instructions were used. Later work by Gamow linked DNA base pair sequences to protein synthesis [15] but it was not until 1961, when Nirenberg and Matthaei demonstrated that cell-free protein synthesis relied upon synthetic or natural polynucleotides [16], that the final link was made. The information held within the linear DNA sequence is replicated every time a cell divides. Replication is possible because of the unique double helical structure of DNA as shown in Fig. 2.7. 

Enzymic Methylation of Natural Polynucleotides Sylvia J. Kerr and Ernest Borek... 

Despite the fact that complexes containing more than two (e.g. 3 6) coordinated nucleic acid bases have been synthesized,as yet no examples of this type of binding have been found in natural polynucleotides, presumably due to structural constraints. 

Fig. 2. Structures of backbones of polynucleotide analogs and natural polynucleotides. If base in question is adenine, then the compounds are 1) poly-9-vinyl-adenine, 2) copolymer of 9-vinyladenine and maleic acid, and 3) polydeoxyadeiqrlate...

Polynucleotide analogs that are polyanions (Fig. 2) have again a number of properties in common. The association of polyanionic analogs with natural polynucleotides is rather weak or, in some cases, even non existent. This is due to a combination of the presence of electronegative diarges and the lack of stereoregularity. Thus, whereas there are as many coulombic repulsions in effect as in cranplexes of nucleic acids, only a few base pairs, which hold different strands tc ether, can be formed. On the other hand, the presence of... 

From various physical and biophysical properties of nucleic acid analogs the most important property for the present purpose is their interaction with nucleic acids. The spectrophotometric methods for detection of complex formation were applied to all combinations of polyvinyl polynucleotide analogs and natural polynucleotides (Fig. 3). In aqueous media hypochromic complexes were formed in combinations where the bases in the polynucleotide and analog were complementary. Poly-l-vinylcytosine is soluble in aqueous-propylene glycol base-pair type complexes were detected there also. An analog of polyinosinate, poly-9-vinylhypoxanthine, is soluble only in solutions of a detergent, sodium dodecylsulfate. This detergent intercalates into the polymer and conveys to it an... 

Fig. 3. Formation of complexes between various combinations of polynucleotide analogs and natural polynucleotides. Abbreviations used poly VA, poly-9-vinyladenine poly VU, poly-l-vinjl-uradl y VC, poly-l-vinylcytosine poly VHX, poly-9-vinylhypoxanthine SDS, sodium dodecyl sulfote...

The sequence-specific binding of synthetic oligonucleotides and analogs to RNA and DNA is studied intensively in the examination of natural polynucleotides and for the development of potential therapeutics [69]. 

Fig-2. Structures of backbones of polynucleotide analogs and natural polynucleotides. If base in question is... 

Covalent coupling to the insoluble matrix is preferable, as before, and also permits the position of attachment in, and orientation of, the polynucleotide chains to be known. As the terminal nucleotides both of synthetic and natural polynucleotides possess structures different from those forming the internal parts of the chain, it is possible to utilize such terminal groups selectively in doing so, overcrowding is avoided, and maximum accessibility is achieved. 

The two types of natural polynucleotides (nucleic acids) are classified according to the sugars they contain. Ribonucleic acid (RNA) contains exclusively P-o-ribose, while the sugar in deoxyribonucleic acid (DNA) is P-2-deoxy-D-ribose. Different nucleic acids can have from around 80 nucleotides (nt), as in transfer RNA (tRNA), to over 10 nucleotide-pairs in a single eukaryotic chromosome. The unit for size of nucleic acid is the base (for single-stranded species) or the base-pair (bp, for double-stranded species), with the unit Kb (thousand base-pairs) and Mb (million base-pairs). Examples of synthetic homopolynucleotides are poly(uridylate) or poly(deoxyadenylate), in poly(U) or poly(dA)... 

Despite numerous attempts,it has not previously been possible to synthesize polynucleotide analogues whose structures and physicochemical properties have a close resemblance to those of natural polymers. Most of the synthesized polynucleotide analogues have exhibited neither good solubilities in water due to the lack of hydrophilic groups nor optical properties due to the absence of sugar moieties on the polymer chain. The alternating sequences between nucleoside and diphosphate, observed in the natural polynucleotides, have also been rarely realized in the syntheas of the analogues. 

Natural polynucleotides contain characteristic sequences of bases in almost infinite variety and often exceed proteins in molecular weight (Table 10.16). DNA molecules from many sonrces have been directly visualised by electron microscopy. 

The choice of phosphate groups for the design of natural polynucleotides is probably no accident. This group can link two mononucleotides and still ionize the resulting negative charge serves to stabilise the diester against hydrolysis and to hold the molecule within a lipid membrane [22]. 

The acetamidate bridge is stable over a large pH range no hydrolysis is found at pH 6-7.5 at 20 C for 7 d. At pH 14 and 37°C, the half-life is 3.4 h (25). However, other properties of these compounds are less advantageous, such as the low solubility in water, the strong tendency to adsorb onto glass and plastic surfaces and, most unfortunately, they do not show any tendency to hybridize with their complementary natural polynucleotides (25). 

Anti-poly A poly U antibodies also react with natural polynucleotides, including reovirus RNA, tRNA and ribosomal RNA from mammalian cells. Inhibition studies have shown that the poly A poly U absorbs all the antibodies reacting with RNA from mouse ascites cells. 

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