Nucleic Acids and Nucleotides

Nucleic acids, the carriers of genetic information, are macromolecules that are composed of and can be hydrolyzed to nucleotide units. Hydrolysis of a nucleotide gives one equivalent each of a nucleoside and phosphoric acid. Further hydrolysis of a nucleoside gives one equivalent each of a sugar and a heterocyclic base. 

The DNA sugar is 2-deoxy-D-ribose. The four heterocyclic bases in DNA are cytosine, thymine, adenine, and guanine. The first two bases are pyrimidines, and the latter two are purines. In nucleosides, the bases are attached to the anomeric carbon (C-1) of the sugar as p-N-glycosides. In nucleotides, the hydroxyl group (-OH) at C-3 or C-5 of the sugar is present as a phosphate ester. 

The primary structure of DNA consists of nucleotides linked by a phosphodiester bond between the 5 -OH of one unit and the 3 -OH of the next unit. To fully describe a DNA molecule, the base sequence must be known. Methods for sequencing have been developed, and, at present, over 150 bases can be sequenced per day. The counterpart of sequencing, the synthesis of oligonucleotides having known base sequences, is also highly developed. 

RNA differs from DNA in three ways the sugar is D-ribose, the pyrimidine uracil replaces thymine (the other three bases are the same), and the molecules are mainly single-stranded. The three principal types of RNA are messenger RNA (involved in transcribing the genetic code), transfer RNA (which carries a specific amino acid to the site of protein synthesis), and ribosomal RNA. 

The genetic code involves sequences of three bases called codons, each of which translates to a specific amino acid. The code is degenerate (that is, there is more than one codon per amino acid), and some codons are stop signals that terminate synthesis. 

This year s nucleotide and nucleic acid literature has been dominated by interest in internucleoside linkages. A number of approaches to novel internucleoside linkages in dimers have been published in addition to stereoselective routes to phosphorothioate and methylphosphonate linkages. In some cases these studies have also extended to the oligonucleotide level. In addition a number of novel nucleotide analogues have been described. One of the most exciting areas in the field of nucleic acid chemistry is the application of in vitro selection techniques and these are reviewed for the first time. 

1 Structure and Conformation of Nucleic Acids and Protein-Nucleic Acid Interactions , ed. M. Sundaralingam and S. T. Rao, University Park Press, Baltimore, 1975. 

Guschlbauer, Nucleic Acid Structure , Springer-Verlag, New York, 1976. 

Taguchi and Y. Mushika, Chem. and Pharm. Bull. Japan), 1975, 23, 1586. 

Mikhailov and J. Smrt, Coll. Czech. Chem. Comm., 1975, 40, 3739. 

An organism s nucleic acids construct its proteins. And, given that the proteins determine how the organism looks and behaves, no job could be more essential. 

Monomer Structure and Linkage Nucleic acids are polynucleotides, unbranched polymers that consist of mononucleotides, each of which consists of an N-containing base, a sugar, and a phosphate group. The two types of nucleic acid, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), differ in the sugar portions of their mononucleotides RNA contains ribose, and DNA contains deoxyribose, in which —H substitutes for —OH on the second C of ribose. 

Most important, each base in one chain pairs with a specific base in the other through H bonding. The essential feature of these base pairs, which is crucial to the structure and function of DNA, is that each type of base is always paired with the same partner A with T and G with C. Thus, the base sequence of one chain is the complement of the sequence of the other. For example, the sequence A—C—T on one chain is always paired with T—G—A on the other A with T, C with G, and T with A. 

Each DNA molecule is folded into a tangled mass that forms one of the cell s chromosomes. The DNA molecule is amazingly long and thin if the largest human chromosome were stretched out, it would be 4 cm long in the cell nucleus, however, it is wound into a rounded structure only 5 nm wide—8 million times shorter  

DNA core. The boxed area is expanded (right) to show how a pyrimidine and a purine always form H-bonded base pairs to maintain the double helix width. The members of the pairs are always the same A pairs with T, and G pairs with C. 

In this year s review, it has only been possible to provide extensive coverage of the mononucleotide area. We hope to include a two-year review of oligo- and poly-nucleotide chemistry and nucleic acid structures in the next volume. 

The papers published during the past year in the field of nucleotide and polynucleotide chemistry have been less remarkable for innovative chemistry than for biochemical application, and sheer volume has necessitated much pruning of the material available. The appearance of a new journal - Nucleic Acid Research - is symptomatic of the increasing publication in this area. Cyclic AMP research, Sutherland s monument, has yielded many new compounds, and no attempt has been made to cover the huge quantity of biochemical and pharmacological data available on these, for which the reader is advised to seek specific reviews. Affinity labelling and affinity chromatography continue to justify the wide research effort they command. 

Chemical Synthesis.—Two new methods for 5 -phosphorylation of nucleosides have been described. In the first, phosphorous acid and mercuric chloride are heated at 80 °C in iV-methylimidazole, and a 2, 3 -0-isopropylidene-protected nucleoside is added. On work-up the 5 -phosphate is obtained in 60— 70% yield. The phosphorylating agent is presumed to be an iV-phosphoryl-AT -methylimidazolium species (1). The second method employs tris-(8-quinolyl) 

The 6 -phosphonate analogue of ribavirin (5 l-jS-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) has been synthesized by oxidizing the 5 -hydroxy- 

When 5 -0-tritylthymidine-3 -phosphate is treated with excess tri-isopropyl benzenesulphonylchloride (TPS) and thymidine, and then deprotected, the trinucleoside monophosphate (7a) is obtained. The 5-bromo- and 5-fluoro-deoxyuridine analogues (7b) and (7c) are prepared similarly. All are resistant to snake venom and spleen phosphodiesterases, and hydrolyse too slowly under physiological conditions for the cytotoxic moiety to be effective. When protected UpU is treated with bis-(4-nitrophenyl) phosphorochloridate, and subsequently with an amine or amino-acid ester, the dinucleoside phosphor-amidates (8) are formed. Although the compounds investigated split the P—N bond under the conditions required for protecting-group removal, the method has potential for the preparation of easily fissionable neutral phospho-triesters. 

Just as proteins are biopolymers made of amino acids, nucleic acids are biopolymers made of nucleotides joined together to form a long chain. Each nucleotide is composed of a nucleoside bonded to a phosphate group, and each nucleoside is composed of an aldopentose sugar linked through its 

Online homework for this chapter can be assigned in Organic OWL. 

CHAPTER 24 biomolecules nucleic acids and their metabolism 

FIGURE 24.1 Structures ofthe four deoxyribonucleotides and the four ribonucleotides. 

Nucleotides are linked together in DNA and RNA by phosphodiester bonds [RO—(P02 l—OR ] between phosphate, the 5 hydroxyl group on one nucleoside, and the 3 -hydroxyl group on another nucleoside. One end of the nucleic acid polymer has a free hydroxyl at C3 (the 3 end), and the other end has a phosphate at C5 (the 5 end). The sequence of nucleotides in a chain is 

sample of DNA purified from MycobacUrium tubercvioiis contain.s 15.1% adenine on a molar basis. What are the percentages of the other bases present  

Double-stranded DNA from most sources contain equimolar amounts of adenine and thymine, and equimolar amounts of guanine and cytosine, that is, A = T and G = C. 

In some organisms, 5-methy cytosine or 5-hydroxymethylcytosine replaces some of the cytosine. The fact that A = T and G C, and that A -f C = G + T (sum of the amino bases equals the sum of the keto bases) together with X-ray diffraction studies led to the idea that DNA is a double helix stabilized by hydrogen bonding (Fig. 2-12). 

Approximately 0.3% of the E. coli chromosome (actually. 0.6% of the coding strand) codes for 23.- rRNA. This corresponds to a segment of MW  

The molecular weights of a ribonucleotide residue and a deoxyribonucleotide residue are about the same (320 and 309, respectively). Since there is a 1 1 coding ratio between DNA and RNA, the E. coli chromosome must contain  

R = P032 nicotinamide adenine dinucleotide phosphate (NADP) 

Nucleic acids are polymers of nucleotides ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Although nucleic acids do not survive for geological periods in sediments (the maximum appears to be c.50kyr under favourable conditions) they are very important they control the self-replication of organisms (and hence provide information on evolutionary relationships) and act as the templates for protein biosynthesis. There are four nitrogen-containing bases 

During cell division the DNA strands separate and act as templates for the construction of new strands. Protein synthesis makes use of various forms of RNA to translate the DNA code into a sequence of amino acids, with each amino acid being coded for by groups of three consecutive bases (e.g. GGA codes for glycine). 

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CHAPTER TWENTY EIGHT Nucleosides Nucleotides and Nucleic Acids... 

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