Nucleotides acid-stable phosphate

Nucleosides and nucleotides are combinations of a base with a sugar. A nucleoside is an N-glycoside formed between a base and a sugar (usually ribose or deoxyribose). A nucleotide is a phosphate ester of a nucleoside. DNA nucleotides are more stable to acid hydrolysis of the glycosidic bond, which is one reason tfrat DNA has superceded RNA as the main genetic storage molecule it is less prone to mutation. 

The measurement of incorporation of radioactive metabolites is frequently used as a response to short and intermediate duration cytotoxicity. Measurements of pH]-thymidine incorporation into DNA and [3H]-uridine incorporation into RNA are the two most common methods of quantifying drug cytotoxicity. Furthermore, [125I]-iododesoxyuridine, a specific and stable label for DNA synthesis, is also employed, as well as measurements of [32P]-phosphate release into medium or incorporation into nucleotides, in addition to the incorporation of [14C]-glucose, [3H]-amino acid, and 45calcium. 

Protection of a phosphate as its 2-phenylthioethyl ester has been shown to be a useful method in the syntheses of phosphate diesters in the nucleotide field. This protecting group is fairly stable to acid and base but treatment with periodate converts it into the sulphoxide (18), which undergoes rapid elimination in aqueous base (Scheme 4). 

Nucleic acids store genetic information. They are polymers whose building blocks (monomers) are the nucleotides, themselves made of three parts—a heterocyclic base, a sugar, and a phosphate ester. In the example below, adenine is the base (shown in black), adenosine is the nucleoside (base and sugar), and the nucleotide is the whole molecule (base + sugar + phosphate). This nucleotide is called AMP—adenosine monophosphate. Phosphates are key compounds in nature because they form useful stable linkages between molecules and can also be built up into reactive molecules by simply multiplying the number of phosphate residues. The most important of these nucleotides is also one of the most important molecules in nature— adenosine triphosphate or ATP. 

The cyclic product is extremely sensitive to moisture (hydrolysis) and was more readily isolated as the cyclic diester. An interesting correlation has been observed the phenyl triesters of high energy cyclic phosphates (cyclic nucleotides, ethylene phosphate) are very reactive species, susceptible to decomposition. On the other hand, the phenyl triesters of low energy cyclic phosphates are stable, crystalline compounds. Hence, for example, the phenyl triester of trimethylene phosphoric acid is a crystalline compound readily prepared in high yield by reaction of 1,3-propanediol with phenyl phosphorodichloridate. 

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