In order to assemble the sequence, addition of each nucleoside requires four chemical reaction steps and each of these reaction steps is expected to be quantitative (100%). In reality, efficiencies of these reaction steps vary from 97 to 99.9% depending on the reagents, nucleoside building blocks (phosphoramidite) and moisture in the solvent. Depending on the efficiency of each nucleoside addit...

Nucleoside diphosphokinase from Salmonella typhimurium has been purified and characterized. In many respects, the enzyme is similar to those from higher organisms in that it has a broad speciCcity for both phosphate donor and recipient and that it functions via a ping-pong mechanism. The enzyme activity of cells is very high at all growth rates but decreases as growth rate increases. Evidence i...

Novel 2'(β)-methyl-5'-deoxyapiose purine phosphonic acid analogues were designed and synthesized from 2-propanone1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Condensation of aldehyde 14 with Wittig reagent [(diethoxyphosphinyl)methylidene] triphenylphosphorane gave the desired nucleoside phosphonate analogues 15. Ammonolysis and hydroly...

We are reporting on the synthesis of fluorescent nucleoside analogs with modified sugar moieties (e.g., sugars other than ribose and 2'-deoxyribose). Four novel derivatives of the fluorescent thymidine analog 6-methyl-3-(beta-D-2'-deoxyribofuranosyl) furano-[2,3-d]pyrimidin-2-one were synthesized via Sonogashira reaction and subsequent copper-catalyzed cycloaddition. These compounds represent p...

An investigational nucleoside analogue drug, viramidine, has recently emerged as a potentially safer alternative to ribavirin for the treatment of hepatitis C viral infection. We have reported that viramidine mainly functions as a prodrug of ribavirin that is enriched in the liver. This in vitro study further explores viramidine's activity against nucleoside phosphorylase, a host enzyme that is...

There are currently six approved nucleoside analogue reverse transcriptase inhibitors. Data are available from clinical trials in human pregnancy for zidovudine and lamivudine, while didanosine and stavudine are under study. Zalcitabine and abacavir have not been studied in pregnant women. Tenofovir disoproxil fumarate is the first acyclic nucleotide analogue reverse transcriptase inhibitor. Th...

Ribavirin is a nucleoside analogue with broad antiviral activity. Here we report the synthesis and biological evaluation of novel ribavirin ProTides designed to deliver the bioactive ribavirin monophosphate into cells. Some of the compounds display activity similar to the parent nucleoside against a range of viruses. Enzymatic, cell lysate and preliminary modeling studies have been performed to...

The addition of naturally occurring polyamines and inorganic ions to an in vitro protein-synthesizing system improved the extent and fidelity of translation. In such an optimized system, regeneration of the nucleoside triphosphates with phosphoenolpyruvate and pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) reduced further the missense error frequency to the in vivo level as ...

1. Pig aortic endothelial and smooth-muscle cells in culture rapidly catabolize exogenous ATP, ADP or AMP. 2. In both cell types catabolism is due to Mg2+-stimulated ectoenzymes. 3. Inhibition and substrate-specificity studies suggest that both cell types possess three distinct ectonucleotidases, namely nucleoside triphosphatase (EC 3.6.1.15), nucleoside diphosphatase (EC 3.6.1.6) and 5'-nucleo...