Nucleosides phosphates

Nucleoside phosphates are protected using triisopropylbenzenesulfonyl chloride in Pyr. ... 

Tu, A. J., Heller, M. J. Structure and Stability of Metal-Nucleoside Phosphate Complexes, in Metal Ions in Biological Systems Vol. 1 (ed. Sigel, H.), p. 1, Marcel Dekker, Inc. New York 1974... 

DNA and RNA are formed of nucleotides. Each nucleotide or nucleoside is composed of a purine or pyrimidine base linked to the 1-position of a ribose sugar in the case of RNA and a 2 -deoxyribose sugar in the case of DNA.155 The 5 position is phosphorylated in the case of a nucleotide, while the nucleoside is not phosphorylated therefore, nucleotides are nucleoside phosphates. Phosphorylation can include one, two, or three phosphate groups. The most familiar example of a phosphorylated nucleotide is phosphorylated adenosine, which occurs as the mono-, di-, and triphosphate (AMP, ADP, and ATP, respectively) and is a principal means of energy storage in biological systems. 

Nucleoside triphosphates are prepared analogously to the diphosphates by the methods a, b, c, and d, representing conversion of a nucleoside phosphoric azolide with inorganic pyrophosphate (Method a), of a nucleoside diphosphoric azolide with inorganic phosphate (Method b), of a phosphoric bisazolide with a nucleoside diphosphate (Method c), and of a diphosphoric bisazolide (bisazolide of pyrophosphoric acid) with a nucleoside phosphate (Method d). 

Another route to such nucleoside diphosphates starts from imidazolides of phosphoric acid monoester and nucleoside phosphates ... 

An estimate of the rate enhancement associated with the intramolecular phosphorylation can be made by using isopropyl p-nitrophenyl methyl-phosphonate as a model for the covalent intermediate formed in the initial step of the reaction of cycloheptaamylose with bis (p-nitrophenyl) me thy 1-phosphonate. The first-order rate constant for the alkaline hydrolysis of isopropyl p-nitrophenyl methylphosphonate at pH 9.86 can be obtained from the data of van Hooidonk and Groos (1970) kun = 1.4 X 10-5 sec-1. This value may be compared with the maximal rate constant for the reaction of cycloheptaamylose with bis(p-nitrophenyl) methylphosphonate— k2 = 1.59 X 10-1 sec-1 at pH 9.86—which must be a minimal value for the rate of the intramolecular phosphorylation. This comparison implies a kinetic acceleration of at least 104 which is similar to rate enhancements associated with the formation of cyclic phosphates from nucleoside phosphate diesters. 

There has been much discussion of complexes between M2+ cations and nucleoside phosphates, which ligands can in principle... 

With a few notable exceptions—such as puromycin and its relatives, psicofuranine and decoynine, and certain 9-alkylpurines-which will be discussed later, purines and their nucleosides must be anabolized to nucleoside phosphates in order to exert their biological effects. This type of metabolic event has been called a lethal synthesis , because it results in the death of cells that carry it out. 

It has been suggested that thioguanine s multistep inhibition, one step of which is the inhibition of phosphoribosylpyrophosphate amidotransferase, results in a profound lowering of the intracellular concentration of guanine nucleoside phosphates and that this depletion causes a marked depression in cellular metabolism that presumably would lead to cell death [91 ]. 

In addition to the analogues listed in Table 2.3, cordycepin [302]. 3 -amino-3 -deoxyadenosine [173], and formycin [303] can inhibit the de novo pathway by blocking the phosphoribosylpyrophosphate amidotransferase. Thus, a number ofpurine analogues—after anabolism to nucleoside phosphates—can act as feedback inhibitors, and this inhibition may be the primary cause of their cytotoxicity. 

The subject of the incorporation of anticancer agents into macromolecules [13] and other compounds [336] has been reviewed. A number of purine analogues are incorporated into nucleic acid, but the incorporation of these compounds requires that they be anabolized to nucleoside mono-, di-, and triphosphates, and it is difficult to separate the metabolic effects of the nucleoside phosphates from the metabolic effects of the fraudulent polynucleotides. 

Ribonucleic acids (RNAs) are polymers consisting of nucleoside phosphate components that are linked by phosphoric acid diester bonds (see p.80). The bases the contain are mainly uracil, cytosine, adenine, and guanine, but many unusual and modified bases are also found in RNAs (B). 

The nucleoside phosphates (1) are not only precursors for nucleic acid biosynthesis many of them also have coenzyme functions. They serve for energy conservation, and as a result... 

The synthesis of purine nucleotides (1) starts from IMP. The base it contains, hypoxanthine, is converted in two steps each into adenine or guanine. The nucleoside monophosphates AMP and CMP that are formed are then phos-phorylated by nucleoside phosphate kinases to yield the diphosphates ADP and GDP, and these are finally phosphorylated into the triphosphates ATP and CTP. The nucleoside triphosphates serve as components for RNA, or function as coenzymes (see p. 106). Conversion of the ribonucleotides into deoxyribo-nucleotides occurs at the level of the diphosphates and is catalyzed by nucleoside diphosphate reductase (B). 

Ribonuc eoside [T CTP synthase 63.4.2 0 Nucleoside phosphate kinase2.Z.4.4... 

Nucleoside phosphates are pivotal in a number of important biological processes, and so the detailed mechanisms of the reactivity of these compounds have been widely studied. A recent study has shown that the major product of hydrolysis of the cyclic thiophosphate analogue 25 varies according to pH as shown in Equation (5). The detailed hydrolysis pathway has implications for the use of such compounds as therapeutic agents <2000EJ01987>. 

Ayengar, P. Gibson, D.M. Sanadi, D.R. Transphosphorylations between nucleoside phosphates. Biochim. Biophys. Acta, 21, 86-91 (1956)... 

---