Guanosine nucleosides

Abacavir (Ziagen) is a guanosine nucleoside analogue indicated for the therapy of HIV-1 infection in adults and children. It is used as part of a multidrug regimen and is available in a fixed-dose combination with zidovudine and lamivudine (Trizivir). It is also used for postexposure HIV infection prophylaxis. 

Mechanism of Action A guanosine nucleoside analog that inhibits hepatitis B viral polymerase, which blocks reverse transcriptase activity. Therapeutic Effect Interferes with viral DNA synthesis. 

The names of the nucleosides formed from these bases and ribose are cytidine, thymidine, uridine, adenosine, and guanosine. Nucleosides formed from deoxyribose are named using the prefix deoxy-, as in deoxythymidine. 

Penciclovir [pen SIK lo veer] is an acyclic guanosine nucleoside derivative that is active against herpes simplex virus Types I and II, and against varicella-zoster virus. Penciclovir is only administered topically (Figure 37.8). Penciclovir is monophosphorylated by viral thymidine kinase, and cellular enzymes form the nucleoside triphosphate, which inhibits herpes DNA polymerase. Penciclovir triphosphate has an intracellular half-life 20 to 30 times longer than does acyclovir triphosphate (see p. 365). Penciclovir is negligibly absorbed from topical application, and is well tolerated. Both healing and pain are shortened approximately one-half day in duration, compared to placebo-treated subjects. 

Entecavir is a guanosine nucleoside with strong antiviral activity. It is also effective in lamivudine-resistant patients. After 48 weeks of treatment comprising a daily dose of 0.5 or 1.0 mg, there was elimination of HBV DNA in 25 — 30% and normalization of the transaminases in 60—70% of lamivudine-resistant patients. Tolerance is good. Entecavir-induced mutants were not detected. (173)... 

The authors suggested that neutrophil dysplasia had resulted from inhibition of guanosine nucleoside synthesis. 

Indications Chronic hepatitis B virus infection Category Antiviral Guanosine nucleoside analog Half-life 24 hours... 

Aciclovir is an analogue of guanosine nucleoside. It is used to treat herpes infections. 

Bam HI cleaves a six-bp palindromic sequence at the phosphodiester bonds between two guanosine nucleosides. Formation of an intrastrand crosslink between the two adjacent guanosine nucleosides inhibits digestion by the enzyme. Another method, termed exonuclease mapping, involves digestion of the... 

Another conformational feature that could be deduced from H NMR studies of all cA-DDP-platinated oligonucleotides containing an embedded d(GpG) sequence is that both guanosine nucleosides retain the anti orientation of the base around the Cl -N9 glycosidic linkage (Figure 9.9). This result was deduced from the lack of a pronounced nuclear Overhauser effect (NOE) between H8 and the HI protons, such as would occur in the syn conformation. An NOE between H8 resonances on the two coordinated nucleosides was observed for... 

Work with a multiple purine mutant could also show that the pyrimidine ring and the ribose side chain of a guanosine nucleoside or nucleotide were incorporated en bloc into riboflavin thus, it was obviously necessary to convert the ribosyl moiety of the guanosine-type precursor into the ribityl side chain of the vitamin by a reduction step. ... 

Acyclovir is an antiviral drug used to treat herpesvirus infection. The basis of its action is that acyclovir resembles part of the guanosine nucleoside and is phosphorylated by the viral enzyme, deoxypyrimidine kinase. The phosphorylated triphosphate form of acyclovir is an inhibitor of the herpesvirus DNA polymerase. A related compound, ganciclovir, H2N works similarly. Uninfected cells do not efficiently phosphorylate acyclovir and ganciclovir, so DNA replication and vims growth are inhibited selectively in infected cells. 

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