Guanosine triphosphate analogs

It is a guanosine analog which probably interferes with the synthesis of guanosine triphosphate, inhibiting capping of viral mRNA and to inhibit the viral RNA-dependent RNA polymerase. 

Glycine (intramolecular proton transfer in water) Okuyama-Yoshida 1998 Guanosine triphosphate and imido/ methylene analogs Cannon 1994... 

Some biosynthetic reactions are driven by the hydrolysis of nucleoside triphosphates that are analogous to ATP—namely, guanosine triphosphate (GTl ), uridine triphosphate (UTP), and cytidine triphosphate (CTP). The diphosphate forms of these nucleotides are denoted by GDP, UDP, and CDP, and the monophosphate forms are denoted by GMP, UMP, and CMP. Enzymes catalyze the transfer of the terminal phosphoryl group from one nucleotide to another. The phosphorylation of nucleoside monophosphates is catalyzed by a family of nucleoside monophosphate kinases, as discussed in Section 9.4. The phosphorylation of nucleoside diphosphates is catalyzed by 7iucleoside diphosphate kinase, an enzyme with broad... 

Ribavirin [13] is a guanosine analog that is intracellularly phosphorylated by the host cell s enzymes. Despite its mechanism is not yet fully elucidated, it apparently interferes with the synthesis of guanosine triphosphate to inhibit capping of viral mRNA and some viral RNA-dependent polymerases. Its triphosphate derivative inhibits the replication of a wide range of RNA and DNA viruses including influenza A and B, parainfluenza, respiratory syncytial virus (RSV), paramyxovirus, HCV and HIV-1. 

The chemical synthesis of adenosine and guanosine triphosphate may be undertaken in a fashion analogous to their biosynthesis phosphorylation of the low energy monophosphate precursors. Phosphorylation is accomplished with phosphoric acid and a coupling (dehydrating) agent, DCC. Use of carbodiimides has already been discussed in connection with peptide bond formation. It will be recalled that reaction proceeds by way of an anhydride... 

Famciclovir is the diacetyl ester prodrug of 6-deoxypencidovir, an acyclic guanosine analog (Figure 49-2). After oral administration, famciclovir is rapidly deacetylated and oxidized by first-pass metabolism to penciclovir. It is active in vitro against HSV-1, HSV-2, VZV, EBV, and HBV. As with acyclovir, activation by phosphorylation is catalyzed by the virus-specified thymidine kinase in infected cells, followed by competitive inhibition of the viral DNA polymerase to block DNA synthesis. Unlike acyclovir, however, penciclovir does not cause chain termination. Penciclovir triphosphate has lower affinity for the viral DNA polymerase than acyclovir triphosphate, but it achieves higher intracellular concentrations. The most commonly encountered clinical mutants of HSV are thymidine kinase-deficient these are cross-resistant to acyclovir and famciclovir. 

It is not the binding of GTP but a slow subsequent conformational alteration that activates the Ga GTP adenylate cyclase complex. This was deduced by study of analogs of GTP, such as guanosine 5 -(P, y-imido) triphosphate (GMP-P-(NH)-P or GppNp), which are... 

Abacavir is the only approved antiretroviral that is active as a guanosine analog. It is initially monophosphorylated by adenosine phosphortransferase. The monophosphate is then converted to (-)-carbovir 3 -monophosphate, which is then phosphorylated to the di- and triphosphates by cellular kinases. Carbovir 5 -triphosphate terminates the elongation of proviral DNA because it is incorporated by the reverse transcriptase into nascent DNA but lacks a 3 -hydroxyl group. 

Biosynthesis of pteridines is based on guanosine 5 -triphosphate transformation. Compounds belonging to folacins arise analogously. 

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