The budding yeast Saccharomyces cerevisiae is unable to incorporate exogenous nucleosides into DNA. We have made a number of improvements to existing strategies to reconstitute an efficient thymidine salvage pathway in yeast. We have constructed strains that express both a nucleoside kinase as well as an equilibrative nucleoside transporter. By also deleting the gene encoding thymidylate syntha...

Purine nucleoside phosphorylase (PNP) deficiency in humans is associated with a severe T cell immunodeficiency. To understand further and exploit this T cell lymphospecificity, we have compared the cytotoxicities and metabolism of deoxyguanosine, the cytotoxic substrate of PNP and of arabinosylguanine, a deoxyguanosine analogue that is resistant to PNP cleavage, in T cell (8402) and B cell (839...

Mutations in the RNase H domain of human immunodeficiency virus type 1 RT have been reported to cause resistance to zidovudine (ZDV) in vitro. However, very limited data on the in vivo relevance of these mutations in patients exist to date. This study was designed to determine the relationship between mutations in the RNase H domain and viral susceptibility to nucleoside analogues. Viruses harb...

Pharmacological inhibition of the cell cycle regulatory kinase Wee1 represents a promising strategy to eliminate cancer cells. Wee1 inhibitors cooperate with chemotherapeutics, e. g. nucleoside analogues, pushing malignant cells from S phase towards premature mitosis and death. However, considerable toxicities are observed in preclinical and clinical trials. A high proportion of tumor cells can...

The available informations on the genotoxic effects in experimental systems of the antiherpesvirus nucleosides aciclovir, penciclovir, ganciclovir, brivudine and cidofovir as well as of the antiretrovirals zidovudine (AZT), lamivudine, zalcitabine (ddC), didanosine and stavudine are reviewed. Furthermore, data on carcinogenic activity of these drugs in laboratory rodents are compiled. Most nucl...

A number of novel phosphate triester derivatives of the anti-viral nucleoside analogue araA have been prepared by a rapid 2-step procedure, not necessitating prior sugar protection. Spectroscopic and lipophilicity data have been collected on these compounds, and they have been assayed with a range of hydrolytic enzymes. The compounds have been found to be highly resistant to hydrolysis at physi...

BACKGROUND Hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) clearance are associated with an improved prognosis in chronic hepatitis B (CHB) patients. These end points are more often achieved with a one-year course of pegylated interferon (PEG-IFN) compared with one year of nucleoside/nucleotide analogue therapy. However, prolonged nucleoside/nucleotide analogue therapy may...

Nucleoside analogue therapy allows safe, long-term suppression of hepatitis B virus (HBV) and is a major milestone in the treatment of chronic hepatitis B. Entecavir has recently been approved by the U.S. Food and Drug Administration and is not only more potent than lamivudine and adefovir, but it is also associated with a very low rate of drug resistance. Peginterferon, which has been shown to...

OBJECTIVE To evaluate genotyping and subtyping in antiretroviral (ARV) naïve and experienced children, as well as drug resistance profiles through genotyping in these children. METHODS This retrospective study assessed ARV-naïve HIV children and HIV children failing highly active antiretroviral treatment (HAART) followed up at Santa Casa de São Paulo. Genotyping was performed using purified p...