Nucleic acid synthesis and

The unique combination of organic chemistry and molecular biology which is nowadays applied in nucleic acid synthesis and analysis led to a great interest in nucleic acid bioorganic chemistry. We give a few examples of recent synthetic endeavours in this field. 

Bredinin, Neosidomycin, and SF-2140. Bredinin (62), isolated from the culture filtrates of Eupenicillium brefeldianum (1,4), inhibits the multiplication of L5178Y, HeLa S3, RK-13, mouse L-ceUs, and Chinese hamster cells. GMP can reverse the inhibition by (62), but (62) is not incorporated into the nucleic acids. The inhibition of nucleic acid synthesis and chromosomal damage in the S and G 2 phases that is caused by (62), is reversed by GMP. It blocks the conversion of IMP to XMP and XMP to GMP. In combination with GMP, (62) interferes with intracellular cAMP levels and thereby inhibits cell division. 

Protecting group, 626 alcohols, 626-628 aldehydes. 717-719 ketones, 717-719 nucleic acid synthesis and, 1114-1115... 

Epirubicin inhibits both DNA and RNA polymerases and thus inhibits nucleic acid synthesis and topoisomerase II enzymes. Epirubicin pharmacokinetics are best described by a three-compartment model, with an a half-life of 4 to 5 minutes, a... 

Virtually all biological reactions are stereospecific. This generalization applies not only to the enzyme-catalyzed reactions of intermediary metabolism, but also to the processes of nucleic acid synthesis and to the process of translation, in which the amino acids are linked in specific sequence to form the peptide chains of the enzymes. This review will be restricted mainly to some of the more elementary aspects of the stereospecificity of enzyme reactions, particularly to those features of chirality which have been worked out with the help of isotopes. 

Folic acid is a vitamin, as we developed in chapter 15. It is a complex molecule that serves as an essential precursor for coenzymes involved in the metabolism of one-carbon units. For example, folic acid-derived coenzymes are critically involved in the biosynthesis of thymidine for nucleic acid synthesis and methionine for protein biosynthesis. The synthesis of both demands donation of a methyl group and they come from folic acid-derived coenzymes. 

M. Hollenstein, C.J. Leumann, Fluorinated olefinic peptide nucleic acid Synthesis and pairing properties with complementary DNA, J. Org. Chem. 70 (2005) 3205-3217. 

Two other features deserve mention. First, there is evidence, especially in the de novo purine pathway, that the enzymes are present as large, multienzyme complexes in the cell, a recurring theme in our discussion of metabolism. Second, the cellular pools of nucleotides (other than ATP) are quite small, perhaps 1% or less of the amounts required to synthesize the cell s DNA. Therefore, cells must continue to synthesize nucleotides during nucleic acid synthesis, and in some cases nucleotide synthesis may limit the rates of DNA replication and transcription. Because of the importance of these processes in dividing cells, agents that inhibit nucleotide synthesis have become particularly important to modern medicine. 

The glycoside/aminoglycoside antibiotics, like the macrolides, exert a bacteriostatic effect due to selective inhibition of bacterial protein synthesis, with the exception of novobiocin (26). The compounds neomycin (27), spectinomycin (28) and streptomycin (29) bind selectively to the smaller bacterial 30S ribosomal subunit, whilst lincomycin (30) binds to the larger 50S ribosomal subunit (cf. macrolides). Apramycin (31) has ribosomal binding properties, but the exact site is uncertain (B-81MI10802). Novobiocin (26) can inhibit nucleic acid synthesis, and also complexes magnesium ion, which is essential for cell wall stability. 

The pentose phosphate pathway serves a variety of functions (1) the production of NADPH for biosynthesis (2) the production of ribose, required mainly for nucleic acid synthesis, and (3) the interconversion of a variety of phosphorylated sugars. 

These findings started a tremendous wave of research interest (a fashion) into the potential role of cytokinins in nucleic acid synthesis (and hence the control of protein synthesis) in plants. Looking back on those years of the early 1960s, the... 

Folic acid Transport of single carbon fragments, especially nucleic acid synthesis and metabolism of some... 

Interference with Nucleic Acid Synthesis and Function... 

If at any time only a little ribose 5-phosphate is required for nucleic acid synthesis and other synthetic reactions, it will tend to accumulate and is then converted to fructose 6-phosphate and glyceraldehyde 3-phosphate by the enzymes transketolase and transaldolase. These two products are intermediates of glycolysis. Therefore, these reactions provide a link between the pentose phosphate pathway and glycolysis. The outline reactions are shown below. 

C. De Waart (1961). Some aspects of phosphate metabolism of Claviceps purpurea II. Relationship between nucleic acids synthesis and ergot alkaloid production. Can. J. Microbiol., 7, 883-892. 

The importance of zinc to growth and development in all forms of life was first established through zinc deficiency studies of microorganisms followed by those in plants and animals see Nutritional Aspects of Metals Trace Elements) The involvement of zinc in a wide variety of metabolic processes including carbohydrate, lipid, protein, and nucleic acid synthesis and degradation paralleled the technical advances in analytical methods that could detect the presence of zinc in minute amounts coupled with advances in the methodology for protein isolation and purification. 

Singh SK, Nielsen P, Koshkin A, Wengel J. LNA (locked nucleic acids) Synthesis and high-affinity nucleic acid recognition. Chem. Commun. 1998 455-456. 

Few studies have compared the toxicity of DMM with MMM. In cell culture, MMM is the more toxic of the two compounds. MMM has been shown to inhibit nucleic acid synthesis and decrease cell viability in cultured cells whereas exposure to DMM has resulted in no significant effects on these parameters. DMM induced chromosomal aberrations and mitotic spindle disturbances to a far lesser extent than the monomethylated form. This underscores the significance of its biotransformation to DMM toxicity. 

With the increase in understanding of viral replication and in particular viral protein and nucleic acid synthesis, and the development of reliable and sophisticated antiviral assays, the young science of antiviral chemotherapy has progressed tremendously over the last 50 years. Acyclovir (Fig. 5.9) was probably the first truly effective and selective... 

In most studies no significant increase in serum uric acid values have been found (Al, T8, Wl), but in some an increase has been reported (B8, S24). The work of Eisen and Seegmiller (E3) is the only report concerned with the metabolic formation of uric acid using radioactive glycine. They did show an increase in the formation of uric acid in extensive psoriasis and a reduction to normal levels with treatment. In addition, the excretion of pseudouridine and uracil was increased in extensive psoriasis (E2) (Table 13). There was a direct correlation in the above studies between the serum uric acid level versus the extent of skin involvement, the excretion of pseudouridine versus the extent of skin involvement, and also the excretion of pseudouridine versus the uric acid excretion (E = 0.81). These findings imply increased nucleic acid synthesis and increased nucleic acid breakdown in the skin, access of the purine breakdown products to the blood stream and from there to the liver ( ) for transformation into uric acid and finally to the kidney for excretion. 

Purine components of nucleic acids, synthesis and transformation of 79CLY730. 

Metabolomics is a quantitative measure of the end products of metabolism in biological tissues and liquid products such as serum and urine (Figure 22.1). Metabolites, in this context, are not the degradation products of the metaboUc and elimination processes associated with exposure to a xenobiotic. They are the normal end products of cellular metabolism of the natural constituents of the tissues and organism such as nitrogenous wastes, energy metabolism, and nucleic acid synthesis and degradation. 

Chapter 17, which focuses on the structure of the nucleic acids, begins with a description of DNA structure and the investigations that led to its discovery. This is followed by a discussion of current knowledge of genome and chromosome structure, as well as the structure and roles of the several forms of RNA. Chapter 17 ends with the description of viruses, macromolecular complexes composed of nucleic acid and proteins that are cellular parasites. In the following chapter (Chapter 18), several aspects of nucleic acid synthesis and function (i.e., DNA replication and transcription) are discussed. Protein synthesis (translation) is described in Chapter 19. 

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