OBJECTIVES To investigate the genotypic and phenotypic effects of in vitro resistance selection with lamivudine and/or the second generation non-nucleoside reverse transcriptase inhibitor (NNRTI) quinoxaline HBY097 using HIV-1 isolates carrying the multi-nucleoside resistance pattern linked to the Q151M mutation. METHODS Virus strains were selected in C8166 cells in the presence of increasing...

BACKGROUND The optimal antiretroviral treatment for patients who have human immunodeficiency virus (HIV) viremia despite treatment with nucleoside reverse-transcriptase inhibitors (nucleoside analogues) remains uncertain. We studied treatment with regimens that combined two nucleoside analogues, at least one of which was new, with the protease inhibitor nelfinavir, the nonnucleoside reverse-tra...

A variety of metabolic intermediates of the glycolytic pathway and tricarboxylic acid cycle have been found to be inhibitors of 6-phosphogluconate dehydrogenase isolated from sheep liver. All nucleoside 5’-triphosphates and 5’diphosphates are inhibitors with Ki values averaging 0.8 mM, nucleoside 5’-monophosphates are also inhibitory with Ki values averaging 6 mu. The 2’and 3’monophosphates of ...

Removal of nucleoside triphosphates from extracts prepared from bacteriophage T7-infected Escherichia coli results in a stringent requirement for added ATP to form infective phage particles by in vitro packaging of bacteriophage T7 DNA. Optimal packaging efficiency was achieved at a concentration of about 1.25 mM. Other nucleoside triphosphates could be substituted for ATP, but none of the comm...

Nucleoside 5'-triphosphates (NTPs) play key roles in biology and medicine. However, these compounds are notoriously difficult to synthesize. We describe a one-pot method to prepare NTPs from nucleoside 5'-H-phosphonate monoesters via pyridinium phosphoramidates, and we used this approach to synthesize ATP, UTP, GTP, CTP, ribavirin-TP, and 6-methylpurine ribonucleoside-TP (6MePTP). Poliovirus RN...

Although the nucleoside analogues fludarabine and chlorodeoxyadenosine have become important therapeutic agents in chronic lymphocytic leukemia (CLL), their effectiveness is limited by drug resistance. Because such resistance is likely to result from impaired drug-induced apoptosis, it is clearly important to understand the mechanisms involved in this process. Whereas p53 can contribute to the ...

Nucleoside derivatives are important therapeutic drugs and the focal point in ongoing search for novel, more potent drug targets. In this study, a new series of pyrimidine nucleoside i.e., uridine ( 1 ) were synthesized via direct method evaluated their antimicrobial potential activity. The title compound was treated with triphenylmethyl chloride pyridine to give 5´- O -(triphenylmethyl)uridine...

Recently, 4'C-ethynyl nucleoside analogues have been identified as highly potent agents against HIV-1, including several multidrug-resistant strains. In contrast to most known nucleoside inhibitors 4'C-ethynyl nucleoside analogues possess a 3'-hydroxyl function. Here we show that the 5'O-triphosphate of 4'C-ethynyl thymidine gets readily incorporated into a nascent DNA strand by HIV-1 reverse t...

amounts of methyl incorporation. Other nucleoside triphosphates besides adenosine triphosphate were capable of sup]x>rting the incorjioration of methyl groups from L-methionine into sRNA. The nonspecificity of the nucleoside triphosphate reaction was shown to be due to an adenosine diphosphokinase reaction and not to nucleoside tri phosphate: L-methionine nucleosidyl transferase activity. Mouse...

Protozoan parasites lack the pathway of the de novo synthesis of purines and depend on host-derived nucleosides and nucleotides to salvage purines for DNA and RNA synthesis. Nucleoside hydrolase is a central enzyme in the purine salvage pathway and represents a prime target for the development of anti-parasitic drugs. The full-length cDNA for nucleoside hydrolase from Leishmania major was clone...