Triphosphate monoester

Prominent amongst the many nucleoside polyphosphates (nucleoside anhydrides) which have been isolated and studied are triphosphate monoesters of type (10.101a) and diphosphate esters of type (10.101b) (R = nucleoside or other organic groups). Many anhydrides of these types have been identified and isolated from natural sources, and some have been obtained by laboratory synthesis. 

Table 7 Comparison of the stability constants (eq. 2) of complexes formed with acetate (Ac ), as a simple mimic of the phosphodiester bridge (Figure 9), mono- (R-MP ), di- (R-DP ), and triphosphate monoesters (R-TP ) in aqueous solution at 25°C and 7 = 0.1 M (NaNOs), together with the corresponding stability differences as they follow from the data listed in neighboring columns" ...

Access to diphosphates (pyrophosphates) and triphosphates is provided through the reaction of phosphoric mono- or diimidazolides with a monoester phosphate. 

Figure 13-1. Classes of enzymes involved in reaction at phosphorus. A and B represent enzyme types that handle phosphoric monoesters and related compounds ( 0 may be an oxygen of a hydroxyl, carboxyl, or phosphoryl group, or the nitrogen of a guanidine group. For simplicity, displacements at the y-phosphoryl groups of nucleosides triphosphates were classified with these reaction). C, D and E represent the enzymes that catalyze transformations of phosphoric diesters (displacements at a or (5 phosphorous groups of nucleoside triphosphates and transfer of pyrophosphates were classified with the reactions of phosphoric diesters).

E Triphosphohydro- lases Triphosphate transfer from a nucleoside triphosphate to water as an acceptor molecule. 3.1.5. Triphosphoric monoester hydrolases... 

TOBACCO [NicoTiANA TABACUM L.) Fractions M-Ia and M-Ib from acid phosphatase of tobacco cells did not hydrolyse phosphate monoesters except para-nitrophenyl phosphate, but hydrolysed phosphoric anhydrides (inorganic pyrophosphate, thiamine pyrophosphate, nucleoside di- and triphosphates). In addition, both fractions hydrolysed bis-para-nitrophenyl phosphate. Fraction M-II, a non-specific acid phosphatase, had broad substrate specificity it hydrolysed pyrophosphate, thiamine pyrophosphate, uridine diphosphate, adenosine triphosphate, uridine triphosphate, and cytidine triphosphate, at rates similar to para-nitrophenyl phosphate (Ninomiya et al., 1977). 

Dicarboxylic acid 5 -monoesters of thymidine and of 5-(2-thienyl)-2 -deoxy-uridine have been prepared as triphosphate mimics. The ester of d4T with citric acid has also been made with the same objective, and more lipophilic bioisosteres 237 and the AZT equivalent have been reported, these being designed to mimic the conformation of the nucleoside triphosphate when complexed to a metal ion. Neither of these last two classes were effective, since all the activity against HIV could be shown to be due to hydrolysis to the parent nucleoside. 

In Figure 9 the general structures for the monoesters of mono-, di-, and triphosphates, symbolized by R-MP, R-DP, and R-TP , respectively, are shown together with the structure of a phosphodiester bridge, (ROlaPO J, as it occurs in the backbone of nucleic acids. This diester of a phosphate group may be... 

Figure 9 Chemical structures of simple monoesters of triphosphate (R-TP ), diphosphate (R-DP ), and monophosphate (R-MP ).

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