The Basics of Nucleic Acids

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

Just as the functioning of nucleic acids depends in part on its overall structure, so does the activity of proteins depend on its overall structure. Protein folding is one of the hot areas today in science. To the synthetic polymer chemist, understanding the influences of factors, basic or fundamental, which produce protein chain folding will allow the creation of new synthetic polymers that possess specifically desired properties. For biochemists, understanding these factors allows us to better understand other factors and to combat particular diseases related to chain folding. 

Free pyrimidines and purines are weakly basic compounds and are thus called bases. They have a variety of chemical properties that affect the structure, and ultimately the function, of nucleic acids. The purines and pyrimidines common in DNA and RNA are highly conjugated molecules (Fig. 8-2), a property with important consequences for the structure, electron distribution, and fight absorption of nucleic acids. Resonance among atoms in the ring gives most of the bonds partial double-bond character. One result is that pyrimidines are planar molecules purines are very nearly... 

The protein portion of the nucleoproteins is basic in nature and being complex in structure may form several types of linkage, depending upon the type of nucleic acid. In gastric digestion or hydrolysis with weak acid, nucleoproteins yield protein and nuclein. The latter in pancreatic digestion or hydrolysis with weak alkali yields additional protein and nucleic add. See also Nucleic Acids. 

The above review shows the progress that has been made in the last 30 years. The prebiotic synthesis of amino acids, purines, pyrimidines, and sugars is understood at a basic level, although more details of the reactions are needed. The polymerization processes are less well understood, and while some of them are plausible it is necessary to work them out in greater detail. The template polymerization reactions are an exciting beginning and may show how genetic information started to accumulate. So far the problem of nucleic acid directed enzyme synthesis has not been dealt with on an experimental level. The problems in this area, which are very difficult, are considered by other speakers in this symposium. 

Inhibition of immune hemolysis by berberine was described by Tanaka (505). Subcutaneous or intravenous injections of berberine either in single doses or repeatedly did not affect the number of erythrocytes, leukocytes, and the hemoglobin level of intact rabbits (506). In rabbits, with anemia induced by phenylhydrazine and toluenedia-mine, berberine had an antianemic effect. Hasegawa and Tanaka (507) did not observe any effect of berberine on the production of plasma cells. It decreased the anticoagulant action of heparin in dog and human blood in vitro (508). Morthland (509) carried out a spectrophotometric study of the interaction of nucleic acids with aminoacridine or with other basic stains including berberine. 

The structure of the DNA molecule is basically determined by nucleic acid base interactions. Although the three-dimensional double helix structure of DNA is influenced by various contributions, the hydrogen bonding in DNA base pairs is of particuar importance. Because it is difficult to obtain gas phase experimental data for isolated base pair characterisation (only a limited number of experimental studies are available [21]) quantum chemical calculations can represent a useful tool to obtain reference data on the structure, properties and interactions of nucleic acid pairs. Theoretical studies can help us to understand the properties of nucleic acids and they are fundamental for verification... 

In this chapter we first summarize the basics needed to consider the interactions of metal ions and complexes with nucleic acids. What are the structures of nucleic acids What is the basic repertoire of modes of association and chemical reactions that occur between coordination complexes and polynucleotides We then consider in some detail the interaction of a simple family of coordination complexes, the tris(phenanthroline) metal complexes, with DNA and RNA to illustrate the techniques, questions, and applications of metal/nucleic-acid chemistry that are currently being explored. In this section, the focus on tris(phenanthroline) complexes serves as a springboard to compare and contrast studies of other, more intricately designed transition-metal complexes (in the next section) with nucleic acids. Last we consider how Nature uses metal ions and complexes in carrying out nucleic-acid chemistry. Here the principles, techniques, and fundamental coordination chemistry of metals with nucleic acids provide the foundation for our current understanding of how these fascinating and complex bioinorganic systems may function. 

Pharmaceutical biotechnology is defined, at its most basic level, as the manipulation of nucleic acids in the production of therapeutic and diagnostic agents. Both DNA and RNA are the fundamental genetic material ... 

Gene therapy is another technique to correct imperfect organ operation, albeit at the basic level of cell function (Le Doux et al., 1995). Gene therapy is the introduction of nucleic acids into cells for a therapeutic effect. Portions of the DNA strand are transferred into the host cell to produce proteins that the unaided cell cannot produce. There are over 4000 known human genetic diseases, and it is likely several hundred of these will be able to be successfully treated with gene therapy (Le Doux et al., 1995). Gene therapy is still in its infancy, and its success is still largely dependent upon chance. Steps in this process involve... 

An extensive literature describes the polarography of nucleic acids. These studies have been basically concerned with the effects of the interfacial electric field on the conformational structure of nucleic acids and this subject is treated in Chapter 3 of this volume. 

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