PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “NUCLEOSIDES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1991

Na(+)-dependent, concentrative nucleoside transport in rat macrophages. Specificity for natural nucleosides and nucleoside analogs, including dideoxynucleosides, and comparison of nucleoside transport in rat, mouse and human macrophages.

The effects of natural nucleosides and various analogs thereof on Na(+)-dependent, concentrative transport of formycin B by cultured rat macrophages were investigated. Concentrative transport is the sole nucleoside transport system of these cells. The results indicated that uridine, 5'-fluorouridine, all natural purine nucleosides, 2-chloroadenosine and 5'-deoxyadenosine are efficient substrates for the transporter. None of nine other pyrimidine nucleosides was transported. 3'-Deoxy-adenosine, 2',3'-dideoxyadenosine, 8-azidoadenosine, tubercidin, 5'-methylthioadenosine 6-mercaptopurine riboside and adenosine arabinoside were either poor substrates or not transported significantly. The substrate activity of some of the natural nucleosides and the lack of substrate activity of 3'-deoxyadenosine, 2',3'-dideoxyadenosine, 8-azidoadenosine and 2',3'-dideoxycytidine were confirmed by direct uptake measurements. No significant concentrative nucleoside transport was detected in cultured human monocytes/macrophages, whereas mouse macrophages possessed both concentrative and equilibrative nucleoside transporters.

Animals↗
PubMed2001

Poly(A) polymerase from Escherichia coli adenylylates the 3'-hydroxyl residue of nucleosides, nucleoside 5'-phosphates and nucleoside(5')oligophospho(5')nucleosides (NpnN).

The capacity of Escherichia coli poly(A) polymerase to adenylylate the 3'-OH residue of a variety of nucleosides, nucleoside 5'-phosphates and dinucleotides of the type nucleoside(5')oligophospho(5')nucleoside is described here for the first time. Using micromolar concentrations of [alpha-32P]ATP, the following nucleosides/nucleotides were found to be substrates of the reaction: guanosine, AMP, CMP, GMP, IMP, GDP, CTP, dGTP, GTP, XTP, adenosine(5')diphospho(5')adenosine (Ap2A), adenosine (5')triphospho(5')adenosine (Ap3A), adenosine(5')tetraphospho(5')adenosine (Ap4A), adenosine(5')pentaphospho(5')adenosine (Ap5A), guanosine(5')diphospho(5') guanosine (Gp2G), guanosine(5')triphospho(5')guanosine (Gp3G), guanosine(5')tetraphospho(5')guanosine (Gp4G), and guanosine(5')pentaphospho(5')guanosine (Gp5G). The synthesized products were analysed by TLC or HPLC and characterized by their UV spectra, and by treatment with alkaline phosphatase and snake venom phosphodiesterase. The presence of 1 mM GMP inhibited competitively the polyadenylylation of tRNA. We hypothesize that the type of methods used to measure polyadenylation of RNA is the reason why this novel property of E. coli poly(A) polymerase has not been observed previously.

Adenosine Monophosphate↗
PubMed2000

Electrogenic uptake of nucleosides and nucleoside-derived drugs by the human nucleoside transporter 1 (hCNT1) expressed in Xenopus laevis oocytes.

The concentrative pyrimidine-preferring nucleoside transporter 1 (hCNT1), cloned from human fetal liver, was expressed in Xenopus laevis oocytes. Using the two-electrode voltage-clamp technique, it is shown that translocation of nucleosides by this transporter generates sodium inward currents. Membrane hyperpolarization (from -50 to -150 mV) did not affect the K(0.5) for uridine, although it increased the transport current approximately 3-fold. Gemcitabine (a pyrimidine nucleoside-derived drug) but not fludarabine (a purine nucleoside-derived drug) induced currents in oocytes expressing the hCNT1 transporter. The K(0.5) value for gemcitabine at -50 mV membrane potential was lower than that for natural substrates, although this drug induced a lower current than uridine and cytidine, thus suggesting that the affinity binding of the drug transporter is high but that translocation occurs more slowly. The analysis of the currents generated by the hCNT1-mediated transport of nucleoside-derived drugs used in anticancer and antiviral therapies will be useful in the characterization of the pharmacological profile of this family of drug transporters and will allow rapid screening for uptake of newly developed nucleoside-derived drugs.

Animals↗
PubMedDate not supplied

Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases.

Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of cellular metabolic processes, as well as for RNA and DNA synthesis. Human tissues contain a thymidylate kinase, a uridylate-cytidylate kinase, five isozymes of adenylate kinase, and several guanylate kinases. Nucleoside monophosphate kinases are also required for the pharmacological activation of therapeutic nucleoside and nucleotide analogs. This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian monophosphate kinases and their role in the activation of nucleoside and nucleotide analogs.

Animals↗
PubMed1984

Identification of the nucleoside transporter in cultured mouse lymphoma cells. Photoaffinity labeling of plasma membrane-enriched fractions from nucleoside transport-competent (S49) and nucleoside transport-deficient (AE1) cells with [3H]nitrobenzylthioinosine.

Plasma membrane-enriched fractions from disrupted S49 lymphoma cells contained high affinity sites for [3H]nitrobenzylthioinosine, a potent and specific inhibitor of nucleoside transport. These sites were absent from similar preparations from AE1 cells, a nucleoside-transport deficient clone derived from the S49 cell line. Reversible binding of [3H]nitrobenzylthioinosine to the S49 membrane preparations was inhibited by adenosine, nitrobenzylthioguanosine, and dipyridamole. Exposure of S49 membrane preparations to UV light in the presence of [3H]nitrobenzylthioinosine resulted in the covalent radiolabeling of a membrane protein(s) which migrated on sodium dodecyl sulfate-polyacrylamide gels with an apparent Mr of 45,000 to 66,000. Labeling of this protein was abolished in the presence of nitrobenzylthioguanosine and markedly reduced in the presence of adenosine and dipyridamole. AE1 membrane proteins were not covalently labeled under these conditions.

Adenosine↗
PubMedDate not supplied

Evidence for separate carriers for purine nucleosides and for pyrimidine nucleosides in the renal brush border membrane.

The aim of the present study was to test if the transport of all nucleosides in rat renal brush border membranes occurs via a common carrier or if specific carriers exist for various groups of nucleosides. We measured the inward transport of radiolabeled nucleosides into brush border vesicles. The effect of unlabeled nucleosides present inside of the vesicles (trans-stimulation) or outside of the vesicles (cis-inhibition) was studied. Uphill influx of a nucleoside into the vesicles could be driven by the efflux of another nucleoside (trans-stimulation) if they were both purines or both pyrimidines but not if one nucleoside was a purine and the other one a pyrimidine. Thus, there exist a carrier that transports various purine nucleosides, and a carrier that transports various pyrimidine nucleosides, but the tested purine nucleosides and the tested pyrimidine nucleosides do not appear to be transported by the same carrier. Uridine and thymidine were similarly potent for the inhibition of cytidine transport whereas uridine was much more potent than thymidine for the inhibition of adenosine transport. This suggests that cytidine and adenosine can use different carriers. Preincubation of the vesicles with N-ethylmaleimide resulted in a marked decrease of the rate of transport of purine nucleosides but it had little effect on the transport of pyrimidine nucleosides. These data are best explained by the presence in the renal brush border membrane of two carriers, one for purine nucleosides, the other one for pyrimidine nucleosides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Nucleosides. 146. 1-Methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6.

The synthesis of 5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-O-acetyl-2'-O-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur (1+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-O-acetyl-2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1- methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.

Animals↗
PubMed1991

Studies on yeast nucleoside triphosphate-nucleoside diphosphate transphosphorylase (nucleoside diphosphokinase). IV. Steady-state kinetic properties with thymidine nucleotides (including 3'-azido-3'-deoxythymidine analogues).

A study of the steady-state kinetics of the crystalline brewer's yeast (Saccharomyces carlsbergensis) nucleoside diphosphokinase, with the magnesium complexes of the adenine and thymidine nucleotides as reactants, has led to a postulated kinetic mechanism which proceeds through a substituted enzyme. This agrees with the earlier conclusions of Garces and Cleland [Biochemistry 1969; 8:633-640] who characterized a reaction between the magnesium complexes of the adenine and uridine nucleotides. An advantage of using thymidine nucleotides as reactants is that they permit accurate, rapid and continuous assays of the enzymatic activity in coupled-enzymatic tests. Through measurements of the initial velocities and product inhibition studies, the Michaelis constants, maximum velocities, and inhibition constants could be evaluated for the individual substrates. Competitive substrate inhibition was encountered at relatively high substrate concentrations, which also permitted an evaluation of their ability to act as 'dead-end' inhibitors. The Michaelis constants for the 3'-azido-3'-deoxythymidine (AzT) analogues were also evaluated and, although these values were only somewhat higher than those of their natural substrates, the Km's for the adenine nucleotides as paired substrates were lower and the Vmax's were drastically reduced. The pharmacological implications of these observations are touched upon and extrapolated to the cases where therapeutic doses of AzT may be employed.

Adenine Nucleotides↗
PubMed1982

Erythrocyte nucleoside transport: asymmetrical binding of nitrobenzylthioinosine to nucleoside permeation sites.

1. Nitrobenzylthioinosine is a potent and specific inhibitor of nucleoside translocation in animal cells. Kinetic and inhibitor binding studies were undertaken to clarify how this inhibitor interacts with the nucleoside transporter from human and nucleoside-permeable type sheep erythrocytes.2. [(3)H]nitrobenzylthioinosine inhibition of zero-trans [U-(14)C]uridine influx into nucleoside-permeable type sheep cells was consistent with simple competitive inhibition (apparent K(i) 1 nmol/l). Analysis of results using total inhibitor levels instead of cell-free inhibitor concentrations did not affect the inhibition pattern, but increased the apparent K(i) value by 5-fold.3. In contrast, [(3)H]nitrobenzylthioinosine was a non-competitive inhibitor of zero-trans [U-(14)C]uridine efflux (apparent Ki 1.5 nmol/l). Dipyridamole, another potent inhibitor of nucleoside translocation, also inhibited zero-trans [U-(14)C]uridine influx in a competitive manner (apparent K(i) 20-40 nmol/l).4. [(3)H]nitrobenzylthioinosine bound to high-affinity sites on cell membranes from human and nucleoside-permeable type sheep cells (apparent K(D) values approximately 1 nmol/l). Binding of inhibitor to these sites was competitively blocked by uridine, a well characterized substrate for the nucleoside transporter (apparent K(i) 1.25 and 0.9 mmol/l, respectively). These apparent K(i) values are close to the apparent K(m) for uridine equilibrium exchange in human erythrocytes.5. Similarly, deoxycytidine was found to be a competitive inhibitor of high-affinity [(3)H]nitrobenzylthioinosine binding activity (apparent K(i) 1.0 and 1.2 mmol/l for human and nucleoside-permeable type sheep cell membranes, respectively). This contrasts with a previous report that this nucleoside had no effect on inhibitor binding activity. Transport studies confirmed that deoxycytidine is a substrate for the erythrocyte nucleoside transporter. Apparent K(m) and V(max) values for [U-(14)C]-deoxycytidine zero-trans influx into human and nucleoside-permeable type sheep cells were comparable to those obtained for [U-(14)C]uridine.6. It is suggested from these results that nitrobenzylthioinosine competes directly with nucleosides for the permeation site of the nucleoside transporter, but that inhibitor binds preferentially to the external membrane surface.

Animals↗
PubMed1982

Nucleoside translocation in sheep reticulocytes and fetal erythrocytes: a proposed model for the nucleoside transporter.

1. Nucleoside transport by fetal erythrocytes from nucleoside-permeable and nucleoside-impermeable type new-born lambs and by reticulocytes from adult sheep was compared with that of mature erythrocytes from adult sheep of the two phenotypes.2. Fetal cells and reticulocytes transported [U-(14)C]uridine rapidly, with little difference between cells from the two types of sheep. Transport occurred by a saturable uptake mechanism with similar properties to that present in mature cells from adult nucleoside-permeable type animals, except for an approximately 100-fold higher V(max).3. This increased translocation capacity was associated with increased numbers of high-affinity [(3)H]nitrobenzylthioinosine binding sites ( approximately 2000-3000 sites/cell compared with approximately 20 sites/cell for mature nucleoside-permeable sheep erythrocytes).4. The calculated transport capacity for each nucleoside translocation site is therefore similar in all cell types (140-180 molecules/site. s at 25 degrees C, assuming that each transport site binds a single molecule of inhibitor). These values compare favourably with turnover estimates for the nucleoside transporter from human and pig erythrocytes.5. Loss of nucleoside transport activity after birth closely paralleled loss of [(3)H]nitrobenzylthioinosine binding sites and the progressive loss of fetal cells from the circulation. Similarly, reticulocyte maturation in vitro was also associated with rapid loss of both nucleoside transport capacity and inhibitor binding activity.6. p-Chloromercuriphenylsulphonate and trypsin had no effect on [(3)H]nitrobenzylthioinosine binding to intact fetal cells. In contrast, both agents markedly inhibited binding to isolated ;ghosts' where both sides of the cell membrane were accessible to reagent. p-Chloromercuriphenylsulphonate inhibition was markedly reduced in the presence of uridine, and reversed by addition of dithiothreitol.7. We conclude that nucleoside transport changes during ontogeny and reticulocyte maturation in the sheep as well as species differences in nucleoside transport capacity are regulated by variations in the numbers of functional transport sites per cell rather than by changes in the activity of a constant number of sites. It is also likely that the nucleoside carrier exhibits chemical asymmetry.8. A simple molecular model of the erythrocyte nucleoside transporter consistent with these and other known properties of the carrier is proposed.

4-Chloromercuribenzenesulfonate↗
PubMed1993

Interaction of nucleoside analogues with the sodium-nucleoside transport system in brush border membrane vesicles from human kidney.

The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na(+)-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na(+)-driven 3H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na(+)-uridine transport was determined. At a concentration of 100 microM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na(+)-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na(+)-uridine uptake with a Ki of 26.4 microM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na(+)-nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The Ki of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside.

Adenosine↗
PubMed1987

Metabolism of pyrimidine bases and nucleosides by pyrimidine-nucleoside phosphorylases in cultured human lymphoid cells.

The anabolism of pyrimidine ribo- and deoxyribonucleosides from uracil and thymine was investigated in phytohemagglutinin-stimulated human peripheral blood lymphocytes and in a Burkitt's lymphoma-derived cell line (Raji). We studied the ability of these cells to synthesize pyrimidine nucleosides by ribo- and deoxyribosyl transfer between pyrimidine bases or nucleosides and the purine nucleosides inosine and deoxyinosine as donors of ribose 1-phosphate and deoxyribose 1-phosphate, respectively: these reactions involve the activities of purine-nucleoside phosphorylase, and of the two pyrimidine-nucleoside phosphorylases (uridine phosphorylase and thymidine phosphorylase). The ability of the cells to synthesize uridine was estimated from their ability to grow on uridine precursors in the presence of an inhibitor of pyrimidine de novo synthesis (pyrazofurin). Their ability to synthesize thymidine and deoxyuridine was estimated from the inhibition of the incorporation of radiolabelled thymidine in cells cultured in the presence of unlabelled precursors. In addition to these studies on intact cells, we determined the activities of purine- and pyrimidine-nucleoside phosphorylases in cell extracts. Our results show that Raji cells efficiently metabolize preformed uridine, deoxyuridine and thymidine, are unable to salvage pyrimidine bases, and possess a low uridine phosphorylase activity and markedly decreased (about 1% of peripheral blood lymphocytes) thymidine phosphorylase activity. Lymphocytes have higher pyrimidine-nucleoside phosphorylases activities, they can synthesize deoxyuridine and thymidine from bases, but at high an non-physiological concentrations of precursors. Neither type of cell is able to salvage uracil into uridine. These results suggest that pyrimidine-nucleoside phosphorylases have a catabolic, rather than an anabolic, role in human lymphoid cells. The facts that, compared to peripheral blood lymphocytes, lymphoblasts possess decreased pyrimidine-nucleoside phosphorylases activities, and, on the other hand, more efficiently salvage pyrimidine nucleosides, are consistent with a greater need of these rapidly proliferating cells for pyrimidine nucleotides.

Cells, Cultured↗
PubMed1987

Nucleoside and nucleobase transport and metabolism in wild type and nucleoside transport-deficient Aedes albopictus cells.

Nucleoside and nucleobase transport and metabolism were measured in ATP-depleted and normal Aedes albopictus mosquito cells (line C-7-10) by rapid kinetic techniques. The cells possess a facilitated diffusion system for nucleosides, which in its broad substrate specificity and kinetic properties resembles that present in many types of mammalian cells. The Michaelis-Menten constant for uridine transport at 28 degrees C is about 180 microM. However, the nucleoside transporter of the mosquito cells is resistant to inhibition by nmolar concentrations of nitrobenzylthioinosine and the cells lack high affinity nitrobenzylthioinosine binding sites. The cells also possess an adenine transporter, which is distinct from the nucleoside transporter. They lack, however, a hypoxanthine transport system and are deficient in hypoxanthine phosphoribosyltransferase activity, which explains their failure to efficiently salvage hypoxanthine from the medium. The cells possess uridine and thymidine phosphorylase activities and, in contrast to cultured mammalian cells, efficiently convert uracil to nucleotides. An adenosine-resistant variant (CAE-3-6) of the C-7-10 cell line is devoid of significant nucleoside transport activity but transports adenine normally. Residual entry of various nucleosides into these cells and of hypoxanthine and cytosine into wild type and mutant cells is strictly non-mediated. The rate of permeation of various nucleosides and of hypoxanthine into the CAE-3-6 cells is related to their hydrophobicity. Uridine permeation into CAE-3-6 cells exhibits an activation energy of about 20 kcal/mol. At high uridine concentrations permeation is sufficiently rapid to partly overcome the limitation in nucleoside salvage imposed by the nucleoside transport defect in these cells.

Adenine↗
PubMed1984

Structural modifications at the 2'- and 3'-positions of some pyrimidine nucleosides as determinants of their interaction with the mouse erythrocyte nucleoside transporter.

Modifications in the sugar moiety of pyrimidine nucleosides may affect their ability to function as permeants of the mouse erythrocyte nucleoside transporter. In this investigation, a number of synthetic uracil and thymine nucleosides which differ from the physiological nucleosides, uridine, deoxyuridine and thymidine, through structural changes at the 2'- and 3'-positions were studied. Interaction of the analogs with the transporter has been assessed in terms of their affinities for an external site on the transporter as well as their abilities to effect trans-acceleration of thymidine efflux. 1-(beta-D-Arabinofuranosyl) uracil (araU) and 1-(beta-D-arabinofuranosyl)thymine (araT) were comparable to thymidine as permeants while nucleosides in which the 3'-hydroxyl was replaced with hydrogen or a halogen had a decreased affinity for the transporter. 3'-Fluoro-3'-deoxy-araU weakly accelerated thymidine efflux while its ribo-isomer and the other 3'-halogeno-3' deoxy-arabino analogs as well as dideoxythymidine inhibited efflux. The absence of 2'- and 3'-carbons in acyclothymidine and acyclouridine strongly decreased the affinities of these nucleosides for the transporter; efflux of thymidine was not accelerated in the presence of these compounds. The conformationally constrained cyclic nucleoside 2,2'-anhydro-araU had a very low affinity for the transporter, and influx of the radiolabeled compound could not be demonstrated. The results suggest that modification at the 3'-position, loss of a portion of the sugar ring, and lack of conformational flexibility are factors which decrease the abilities of some pyrimidine nucleosides to function as permeants. It is suggested that combined effects of substituents which play a role in determining nucleoside conformation should be considered in assessing structural requirements for permeants of the transporter.

Animals↗
PubMed1992

3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity of [2'-5'-bis-O-(tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranose]-3'-spiro-5"-[4"-amino-1",2"-oxathiole 2",2"-dioxide] (TSAO) pyrimidine nucleosides.

A series of 3'-spiro nucleosides have been synthesized and evaluated as anti-HIV-1 agents. Reaction of O-mesylcyanohydrins of furanos-3'-ulosyl nucleosides with base afforded [1-[2',5'-bis-O- (tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranosyl]]-3'-spiro-5"- [4"-amino-1",2"-oxathiole 2",2"-dioxide] derivatives of thymine, uracil and 4-N-acetylcytosine 11 and 12. Desilylation of 11 and 12 gave the full deprotected 3'-spiro xylo- and ribofuranosyl nucleosides 13 and 14 or the partially 5'-O-deprotected-3'-spiro beta-D-xylo- and -ribo-nucleosides 15 and 16, or 2'-O-deprotected-3'-spiro beta-D-ribo-nucleoside 17. 2'-Deoxygenation of 17 afforded 2'-deoxy-3'-spiro beta-D-erythro-pentofuranosyl derivative 18. These 3'-spiro derivatives were evaluated for their anti-HIV-1 activity. All 3'-spiro nucleosides having a xylo configuration did not show any anti-HIV-1 activity. 3'-Spiro ribo-nucleosides with none or only one silyl group at C-2' or C-5' or the 2'-deoxy derivative were also inactive at subtoxic concentrations. However, 3'-spiro ribo-nucleosides having two silyl groups at C-2' and C-5' were potent and selective inhibitors of HIV-1. None of the nucleoside analogues that showed anti-HIV-1 activity proved inhibitory to the replication of HIV-2 or SIV.

Antiviral Agents↗
PubMed2000

Acylphosphatase possesses nucleoside triphosphatase and nucleoside diphosphatase activities.

We have demonstrated that acylphosphatase possesses ATP-diphosphohydrolase (apyrase-like) activity. In fact, acylphosphatase first catalyses the hydrolysis of the gamma-phosphate group of nucleoside triphosphates, and then attacks the beta-phosphate group of the initially produced nucleoside diphosphates, generating nucleoside monophosphates. In contrast, it binds nucleoside monophosphates but does not catalyse their hydrolyses. The calculated k(cat) values for the nucleoside triphosphatase activity of acylphosphatase are of the same order of magnitude as those displayed by certain G-proteins. An acidic environment enhances the apyrase-like activity of acylphosphatase. The true nucleotide substrates of acylphosphatase are free nucleoside di- and triphosphates, as indicated by the Mg(2+) ion inhibition of the activity. We have also demonstrated that, although nucleoside triphosphates are still hydrolysed at pH 7.2 and 37 degrees C, in the presence of millimolar Mg(2+) concentrations this occurs at a lower rate. Taken together with the previously observed strong increase of acylphosphatase levels during induced cell differentiation, our findings suggest that acylphosphatase plays an active role in the differentiation process (as well as in other processes, such as apoptosis) by modulating the ratio between the cellular levels of nucleoside diphosphates and nucleoside triphosphates.

Acid Anhydride Hydrolases↗
PubMed1980

Nucleoside transport in human and sheep erythrocytes. Evidence that nitrobenzylthioinosine binds specifically to functional nucleoside-transport sites.

Nitrobenzyl[35S]thioinosine binding and nitro[3H]benzylthioinosine binding to nucleoside-permeable and nucleoside-impermeable sheep erythrocyte membranes was investigated, and compared with that found for human erythrocytes. High-affinity nitrobenzylthioinosine-binding sites (apparent KD congruent to 1 nM) were present on human and nucleoside-permeable but not nucleoside-impermeable sheep erythrocyte membranes (8400 and 18 sites/cell for human and sheep nucleoside-permeable sheep erythrocytes was displaced by nitrobenzylthioguanosine and dipyridamole. Uridine, inosine and adenosine inhibited binding. The smaller number of nitrobenzylthioinosine sites on nucleoside-permeable cells compared with human erythrocytes corresponded to a considerably lower Vmax. for uridine influx in these cells (0.53 X 10(-20) mol/cell per s at 25 degrees C compared with 254 X 10(-20) mol/cell per s). It is suggested that high-affinity nitrobenzylthioinosine binding represents a specific interaction with functional nucleoside-transport sites. The uridine-translocation capacity for each transport site at 25 degrees C is 180 molecules/site per s for both nucleoside-permeable sheep cells and human erythrocytes (assuming a 1:1 interaction between nitrobenzylthioinosine and the nucleoside-transport system).

Animals↗