The Building Blocks of Nucleic Acids

3 Interference with Nucleic Acid Synthesis and Function 

Oligonucleotides are nucleic acid polymers. Each nucleic acid is assembled from a sugar, a nitrogenous heterocyclic base, and a phosphate. The specific identity of the sugar and base determines the type of nucleic acid, which in turn determines the structure and function of the oligonucleotide. 

DNA contains the full genetic blueprint for an organism. Every enzyme, receptor, and structural protein is encoded by DNA in subsections called genes. Collectively, all the genes of an organism comprise its full genome. For humans, the full genome consists of over 3 billion nucleotide pairs.2 

Additional nucleic acids as their triphosphates may add to the 3 end of the existing oligonucleotide. This entire process is catalyzed and controlled by DNA polymerases, a family of enzymes that can replicate and repair DNA. The synthesis of DNA is always performed in the 5 to 3 direction.2 Furthermore, oligonucleotide strands are written with the letters of the nucleic acid monomers, starting from the 5 end. Oligonucleotide abbreviations should be read with an open mind because the literature contains many slightly different notation styles. 

Because of the importance of DNA and the need to keep it as safe and protected as possible, DNA is found only in the restricted environment of the nucleus. Furthermore, it is wound into a compact form to minimize the possibility of damage. When the genetic information of DNA is needed elsewhere in the cell, DNA is partially unwound and 

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Nucleotides are the building blocks of nucleic acids their structures and biochemistry were discussed in chapter 23. When a 5 -phosphomononucleotide is joined by a phosphodiester bond to the 3 -OH group of another mononucleotide, a dinucleotide is formed. The 3 -5 -linked phosphodiester intemucleotide structure of nucleic acids was firmly established by Lord Alexander Todd in 1951. Repetition of this linkage leads to the formation of polydeoxyribonucleotides in DNA or polyribonucleotides in RNA. The structure of a short polydeoxyribonucleotide is shown in figure 25.3. The polymeric structure consists of a sugar phosphate diester backbone with bases attached as distinctive side chains to the sugars. 

Levene showed that nucleotides are the building blocks of nucleic acids. 

Other successes were reported in the early years of research on the origin of life. Perhaps the most notable achievement was by the laboratory of Juan Oro. They showed that the simple chemical hydrogen cyanide would react with itself to yield a number of products including adenine, which is a component of one of the building blocks of nucleic acids. The result cracked open DNA and RNA as targets for chemical investigation... 

Figure 5.5 Amino acids, the building blocks of proteins, are far simpler molecules than nucleotides, the building blocks of nucleic acids.

Nucleotides form the building blocks of nucleic acids. A nucleotide is made up of a phosphate, a sugar, and an amine "base." An example is shown below ... 

Carhonaceous chondrites are also of interest because of the fascinating mix of relatively complex organic molecules they contain. Scientists have now discovered both amino acids and nitrogen bases in meteorites. Amino acids are the compounds of which proteins are made, and nitrogen bases are one of the building blocks of nucleic acids such as DNA and RNA. Researchers have found 92 amino acids in just one meteorite, the Murchison meteorite that fell about 60 miles (100 km) north of Melbourne, Australia, in 1969. Of these 92 amino acids, only 19 are found on Earth. Studies of other meteorites have shown that the Murchison results are not unique. In fact, amino acids occur in a number of carhonaceous chondrites. 

Control of parasitic invasions has been successfully achieved with compounds that inhibit key enzymes in pathways vital to the biosynthesis of the building blocks of nucleic acids in these pathogenic microorganisms. This results in their reproductive suppression or death. An alternative mechanism can also exist, particularly if the inhibitor has a close chemical similarity to the enzyme s normal substrate (metabolite). Such an analog compound may still be affected by the enzyme, resulting in a false structural component, which if incorporated into the essential biopolymer at all, will lead to nonfunctioning (or errant) DNA or RNAs. Such drugs are referred to as antimetabolites. They... 

In addition to these we need to mention a small group of metabolites that belong structurally with the building blocks of nucleic acids but which have major metabolic functions that are quite separate from their relationship to nucleic acids. These are the adenosine phosphates two of these, adenosine 5 -triphosphate and adenosine 5 -diphosphate, participate in many metabolic reactions (more, indeed, than any other substance, aside from water) a third, adenosine 5 -monophosphate, participates in relatively few reactions but affects many enzymes as an inhibitor or as an activator. These names are cumbersome for everyday use and biochemists refer to them nearly aU of the time as ATP, ADP, and AMP, respectively. In animals, the ATP needed for driving all the functions of the cell is generated in small compartments of cells called mitochondria. For the purposes of this book we shall not need to know any details of how mitochondria fulfill their functions, but we do need to know that they exist, because we shall meet them again in a quite different context it turns out that in most organisms mitochondria contain small amounts of their own DNA, and this allows some special kinds of analyses. Adenosine, the skeleton from which ATP, ADP, and AMP are built, has a separate importance as one of the four bases that define the sequence of DNA. 

Nucleotide Gompounds with a nitrogenous base linked to a pentose phosphate that form the building blocks of nucleic acids such as DNA. 

This energy can be used to drive nonspontaneous reactions in the body. However, a means is necessary to transport the energy released by glucose metabolism to the reactions that require energy. One way, shown in T HGURE 19.19, involves the interconversion of adenosine triphosphate (ATP) and adenosine diphosphate (ADP), molecules that are related to the building blocks of nucleic acids. The conversion of ATP to ADP releases free energy (AG" = —30.5kJ) that can be used to drive other reactions. 

The basic structure of the building blocks of nucleic acids renders them inherently of no use for direct electronic properties. In contrast, the amide bond exhibits an important contribution of a double bond character, especially when it is electronically coupled to aromatic moieties [171,172]. 

Nucleic acids are linear, chain-like macromolecules that were first isolated from cell nuclei. Hydrolysis of nucleic acids gives nucleotides, which are the building blocks of nucleic acids, just as amino acids are the building blocks of proteins. A complete description of the primary structure of a nucleic acid requires knowledge of its nucleotide sequence, which is comparable to knowing the amino acid sequence in a protein. 

The building blocks of nucleic acids are themselves composed of certain organic bases linked to either ribose or deoxyribose, both of which are sugar molecules. In this short subsection, we will briefly discuss the structure of monosaccharides, or sugars, before we launch into the structure of nucleic acids. 

The building blocks of nucleic acids are called nucleotides (nt). Each nucleotide consists of three parts (Fig. 1.5) (i) a nitrogen-containing heterocyclic base (pyrimidine or purine base), (ii) a pentose (C5 sugar), and (iii) a molecule of phosphoric acid. 

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