Polynucleotides structure

Platinum complexes probes of polynucleotide structure and antitumour drugs. S. J. Lippard, Acc. Chem. Res., 1978,11, 211-217 (56). 

It is interesting to note that a preliminary report ascribes a polynucleotide structure to the enzyme cysteinylglycinase.166... 

Figure 3.5 The basic polynucleotide structure as shown in (a) outline form and (b) in chemical detail. The 5 end of the chain is defined by lacking a nucleotide attached to the first sugar s carbon number 5 the 3 end lacks a nucleotide attached to the carbon number 3 of the last sugar in the backbone...

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

The phosphorus- and nitrogen-containing materials that came to be known as nucleic acids were first isolated from cells around 1870 by Friedrich Miescher but were long regarded as something of a curiosity.1 Nevertheless, the structures of the monomer units, the nucleotides, were established by 1909 and the correct polynucleotide structure of the chains of DNA and RNA was proposed by Levene and Tipson in 1935.2/3... 

The reactivity of metal ions is not always the same with DNA and RNA. One reaction that is exclusive to RNA is depolymerization of the polynucleotide structure by the cleavage of the phosphodiester bonds. This depolymerization reaction, as with other RNA hydrolyses, can be induced by metal hydroxides, Zn being one of the most effective. A simple mechanism is that the Zn" chelates to the phosphate group and the 2 -hydroxyl group of ribose (the 2 -group is absent in DNA). Electron withdrawal by the Zn ion then weakens the phosphodiester linkage. Such a mechanism, however, does not take into account the observed influence of the nature of the adjacent base and the formation of metal-dependent products. Pb is also an effective catalyst in site-specific depolymerization of tRNA. In this case the metal has been shown to bind to the bases with only weak interactions with phosphate groups. The catalytic action has been interpreted in terms of nucleophilic attack by a metal-bonded hydroxide ion.134 This may have implications for the mechanisms of other metal ions active in this reaction. 

There is another reason for believing that life evolved at low temperatures, whether in the oceans or in lakes. All of the template-directed reactions that must have led to the emergence of biological organization take place only below the melting temperature of the appropriate organized polynucleotide structure. These temperatures range from 0°C, or lower, to perhaps 35°C, in the case of polynucleotide-mononucleotide helices. 

The formation of the polynucleotide structure poly(I) is strikingly cation dependent, and relates to the size of the alkali metal cation in the central cavity. Lithium and cesium cations are too small or too large respectively to bind effectively. Na+ occupies a site that is 2.2 A away from four carbonyl oxygens, while K+ is able to occupy a site 2.8 A away from eight carbonyl oxygens.101... 

V. Brabec and G. Dry hurst, Electrochemical behaviour of natural and biosynthetic polynucleotides at the pyrolytic graphite electrode. A new probe for studies of polynucleotide structure and reactions, J. Electroanal. Chem., 89 (1978) 161-173. 

Some New Polynucleotide Structures and Some New Thoughts About Old Structures... 

Zmudzka B, Shugar D (1969) Poly 2 -0-methylcytidylic acid and the role of the 2 -hydroxyl in polynucleotide structure. Biochem Biophys Res Commun 37 895 -901... 

The existence of base stacking interaction for poly-VUr was also suggested from UV spectra25). At pH 12, the value of hypochromicity for poly-VUr was 29 to 51 % as compared to 1-ethyluradl. For poly-U solution, the value is only a few percent at room temperature while at lower temperature, about 30% of hypochromicity is observed which is attributed to the formation of a stacked helical polynucleotide structure. It seems therefore likely that the high value of hypochromicity observed for poly-VUr solution may be due to base stacking interactions. 

Possible Effects of Polynucleotide Structures on Metal-Ion Binding 3... 

Metal Binding Can Induce Conformational Changes of Polynucleotide Structures 24... 

POSSIBLE EFFECTS OF POLYNUCLEOTIDE STRUCTURES ON METAL-ION BINDING... 

METAL BINDING CAN INDUCE CONFORMATIONAL CHANGES OF POLYNUCLEOTIDE STRUCTURES... 

An interaction of metal ions with phosphates usually leads to stabilization of polynucleotide secondary and tertiary stmctures, depending on the metal ions and their concentrations, whereas base binding or chelating base and phosphate by the same metal ion may result in destabilization, conformational change, or denaturation of the polynucleotide structures (see also Sections 3.3.1 and 3.3.2). However, phosphate-specific binding can also induce significant conformational changes in DNA structure. The mechanisms of the latter structural interconversions are... 

Table 5. Interferon induction by synthetic polynucleotides structural requirements...

Ray J, Manning GS. Theory of delocalized ionic binding to polynucleotides structural and excluded-volume effects. Biopolymers 1992 32 541-549. 

A DNA macromolecule is able to store or encode an enormous quantity of genetic information by virtue of its extensive polynucleotide structure (Aktipis, in Devlin, 1986, p. 798ff). The analogy is to proteins, which are made up of a chain of amino acids joined by what are called peptide bonds, to yield the polymer or macromolecule. Thus, there is a similarity between the structures of polynucleotides and proteins, which is a factor in transmitting genetic information between the DNA and protein macromolecules, with RNA serving as the medium or intermediate. 

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