New homo- and hetero-P(1),P(2)-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3'-fluoro-2-thiothymidine, 3'-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5-propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P(1),P(2)-dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 ce...

Phosphorylation of deoxycytidine analogs by cellular enzymes is a prerequisite for the activity of these compounds. We have investigated the kinetic parameters for the phosphorylation of 1-beta-D-arabinofuranosylcytosine (araC) and 2', 2'-difluorodeoxycytidine (dFdC) to their diphosphate forms catalyzed by human UMP-CMP kinase. We cloned the cDNA of this enzyme to enable characterization of the...

The kinetics of [3H]inositol phosphate metabolism in agonist-activated rat parotid acinar cells were characterized in order to determine the sources of [3H]inositol monophosphates and [3H]inositol bisphosphates. The turnover rates of D-myo-inositol 1,4,5-trisphosphate and its metabolites, D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,3,4-trisphosphate, were examined following the additio...

An assay for measuring 3’,5’-cyclic nucleotide phosphodiesterase activity over a wide range of substrate concentrations has been described. The ratio of cyclic adenosine 3’,5’monophosphate (cyclic AMP) to cyclic guanosine 3’,5’monophosphate (cyclic GMP) hydrolysis varied several fold among crude subcellular fractions from bovine and rat heart when measured at micromolar but not millimolar subst...

The hypermodified dinucleoside monophosphates, uridylyl(3’-5’)-N-[9-(~-~-ribofuranosyl)purin-6ylcarbamoyl]threonine (Upt6A), adenylyl(3’-5’)-N6-(A2isapenteny1)adenosine (ApihA), adenylyl( 3’-5’)-N6-( A2-isopentenyl)-2-methylthioadenosine (Apms2i6A), and adenylyl(3’-5’)-l ,N6-ethenoadenosine (AptA, a synthetic model for adenylyl(3’-5’)wybutosine, ApyW), which represent the most common sequences ...

PtdIns3P is recognized as an important player in the control of the endocytotic pathway and in autophagy. Recent data also suggest that PtdIns3P contributes to molecular mechanisms taking place at the plasma membrane and at the midbody during cytokinesis. This lipid is present in low amounts in mammalian cells and remains difficult to quantify either by traditional techniques based on radiolabe...

ÐModi®ed guanosine monophosphates have been employed to introduce various functional groups onto RNA 50-ends. Applications of modi®ed RNA 50-ends include the generation of functionalized RNA libraries for in vitro selection of catalytic RNAs, the attachment of photoanity-tags for mapping RNA±protein interactions or active sites in catalytic RNAs, or the nonradioactive labeling of RNA molecules...