Nucleic synthesis

Trichloroethanol may be used analogously. The 2,2,2-trichloroethyl (Tee) group is best removed by reduction with copper-zinc alloy in DMF at 30 °C (F. Eckstein, nucleic acid synthesis see section 4.1.1. 

The fundamental problem of oligodeoxyribonucleotide synthesis is the efficient formation of the intemucleotidic phosphodiester bond specifically between C-3 and C-5 positions of two adjacent nucleosides. Any functional group (NH of nucleic base the other OH of deoxy-... 

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. 

DNA polymerase enzymes all synthesize DNA by adding deoxynucleotides to the free 3 -OH group of an RNA or DNA primer sequence. The identity of the inserted nucleotide is deterrnined by its abiHty to base-pair with the template nucleic acid. The dependence of synthesis on a primer oligonucleotide means that synthesis of DNA proceeds only in a 5%o V direction if only one primer is available, all newly synthesized DNA sequences begin at the same point. 

As an activator of the phosphokinases, magnesium is essential in energy-requiring biological processes, such as activation of amino acids, acetate, and succinate synthesis of proteins, fats, coen2ymes, and nucleic acids generation and transmission of nerve impulses and muscle contraction (67). 

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Oxanosine. Oxanosiae (50), which is isolated from S. capreolus (1,148), is a potent inhibitor of GMP synthetase and nucleic acid synthesis (149,150). 

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. 

Quinacrine concentrates in the scolex of the parasite and causes the muscles needed for holding onto the intestinal wall to relax. The worms are stained yellow and pass from the body, still aUve. Quinacrine can intercalate with DNA and inhibit nucleic acid synthesis. It creates fluorescent bands in deoxyadenylate—deoxythmidylate-rich regions of DNA and has been used as a stain in the study of human genetics. 

It iaterferes with the synthesis of the hyphal walls, the biosynthesis of nucleic acids, and the synthesis of chitin. The iateraction with microtubules has also been described. The sensitivity of a cell seems to depend particularly on the abiUty to form griseofulvin—nucleic acid complexes. Further information concerning griseofulvin is available (21). 

The first are competitors of PABA (p-aminobenzoic acid) and thus intermpt host de novo formation of the tetrahydrofoUc acid required for nucleic acid synthesis. Examples of dmgs that fall into this group are the sulfones and sulfonamides. The most weU-known of the sulfones is dapsone (70, 4,4 -diaminodiphenyl sulfone, DDS), whose toxicity has discouraged its use. Production of foHc acid, which consists of PABA, a pteridine unit, and glutamate, is disturbed by the substitution of a sulfonamide (stmcturally similar to PABA). The antimalarial sulfonamides include sulfadoxine (71, Fanasd [2447-57-6]) sulfadiazine (25), and sulfalene (72, sulfamethoxypyrazine [152-47-6] Kelfizina). Compounds of this group are rapidly absorbed but are cleared slowly. 

Nucleic acids are the molecules of the genetic apparatus. They direct protein biosynthesis in the body and are the raw materials of genetic technology (see Genetic engineering). Most often polynucleotides are synthesized microbiologicaHy, or at least enzymatically, but chemical synthesis is possible. 

The classification of these dmgs as antimetaboHtes stems from the mode of action as antagonists to the natural metaboHc processes leading to either DNA, RNA, or proteiu synthesis (13) (see Nucleic acids Proteins). They either inhibit function of a key en2yme involved in protein synthesis or are recmited into the cell division process as DNA synthesis terrninators. For example, methotrexate (8) is a foHc acid [59-30-3], antagonist and... 

Uracil is used more effectively, in nucleic acid synthesis within a rat hepatoma than in normal liver. This observation appears to have stimulated the synthesis of 5-fluorouracil (1027) as an antimetabolite mainly because the introduction of a fluorine atom involves a minimal increase in size. In the event, 5-fluorouracil did prove to have antineoplastic activity and it is now a valuable drug for treatment of tumors of the breast, colon or rectum, and to a lesser extent, gastric, hepatic, pancreatic, uterine, ovarian and bladder carcinomas. As with other drugs which interfere with DNA synthesis, the therapeutic index is quite low and great care is required during treatment (69MI21301). 

Friedlander synthesis, 2, 445 Acridine-1,8-diones, hexahydro-synthesis, 2, 482 Acridine Orange colour and constitution, 1, 346 nucleic acid stain, 1, 179... 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions... 

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