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Results for “Polyribonucleotides”

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At least 19 recordsLinked to original sources

PubMed1978

Enhancement by double-stranded polyribonucleotides of production by cultured mouse peritoneal macrophages of differentiation-stimulating factor(s) for mouse myeloid leukaemic cells.

Mouse peritoneal macrophages release a factor(s) that stimulates differentiation of a mouse myeloid leukaemic cell line into mature granulocytes and macrophages. Treatment of the macrophages with the synthetic double-stranded polyribonucleotides poly(I).poly(C) and poly(A).poly(U) resulted in enhanced release of the factor into the culture medium. The effect was maximal after treatment with polyribonucleotides for 1 h, and the optimal dose of poly(I).poly(C) was 50 microgram/ml. The single-stranded polyribonucleotides poly(I) and poly(C) at the same concentration were far less effective. The differentiation-stimulating factor was detected not only in the cultured medium but also in the cell lysate. Exposure of macrophages to poly(I).poly(C) enhanced the total activity of the factor in both the culture medium and the cell lysate. The effect of this compound was blocked by the presence of cycloheximide. These results suggest that double-stranded polyribonucleotides enhance production of the differentiation-stimulating factor by peritoneal macrophages.

Animals↗

PubMed1992

[Biological actions and therapeutic perspectives of double stranded polyribonucleotides: a reappraisal].

Double-stranded polynucleotides, which are composed of two complementary homopolyribonucleotides containing no genetic information, are synthetic molecules capable of mimicking the action of natural double-stranded RNA or viral RNA on cells. Double-stranded polyribonucleotides act as an alarm system alerting the cell to the presence of an external aggression, e.g. a viral attack. In addition, polyribonucleotides have a more active function in that they trigger cell defense processes through activation of a family of genes, of which some encode cytokines, activation of cytoplasmic enzymes involved in antiviral mechanisms or signal transduction, and activation of nonspecific immune responses. Double-stranded polyribonucleotides containing one mismatched base pair per helix have been found to be especially interesting. The best known example is poly(I).poly(C12U), also called ampligen. Poly(I).poly(C12U) is capable, in experimental models, of limiting the development of viruses (including HIV), reducing tumor growth, eliminating metastases, and, according to one report, preventing steady declines in T-cell counts in HIV-positive patients. Therapeutic doses used in the USA as an experimental drug induced little toxicity. In vitro, poly(I).poly(C12U) acts synergistically with interferon, interleukin 2 or AZT, suggesting that these latter drugs may be effective in lower, less toxic doses when used in combination with poly(I).poly(C12U). The therapeutic activity of poly(I).poly(C12U) holds promise. More extensive prospective studies of this agent are warranted.

Cytomegalovirus Infections↗

PubMedDate not supplied

[Comparative antiviral and interferonogenic activity of synthetic polyribonucleotide complexes of poly(I).poly(C) and poly(G).poly(C) in different cell systems].

The antiviral and interferon-inducing activity of synthetic polyribonucleotide complexes poly(I)-poly(C) and poly(G)-poly(C) was studied in chick embryo, mouse embryo and rabbit kidney cell cultures. In chick embryo cell cultures both polyribonucleotides had similar antiviral activities. The interferon-inducing activity was more marked in poly(G)-poly(C) than in poly(I)-poly(C). In the other two cell cultures poly(I)-poly(C) was considerably superior in both activities. The revealed differences in the comparative activity of the polyribonucleotides in relation to the kind of tissue culture were not associated with differences between them in toxicity, sensitivity to pancreatic RN-ase or with possible differences in the duration of the contact with cells necessary for the achievement of the antiviral effect.

Animals↗

PubMed1979

Affinity of human leukocyte interferon for polyribonucleotides.

Human leukocyte interferon (HL-IF)binds to AGPOLY(A)TM, AGPOLY(U)TM and AGPOLY(I)TM. The bound interferon could be displaced from all three polyribonucleotides by including sodium chloride in the eluant. The nature of interaction of HL-IF with polyribonucleotides is electrostatic and not hydrophobic since its binding was not prevented in the presence of 50% ethylene glycol. The binding of HL-IF on AGPOLY(I)TM is stronger at lower pH since an increase in ionic strength is required to displace it.

Binding Sites↗

PubMed1977

Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine.

Urine contains nondialyzable inhibitors of calcium oxalate crystal growth. We have pursued the hypothesis that these inhibitors may, in part, be acidic peptides and polyribonucleotide fragments. Homopolyribonucleotides and RNA inhibit calcium oxalate crystal growth at 5 x 10(-6) M of constituent ribonucleotide, whereas the monomer nucleotides are inactive at 10(-4) M. Poly-L-aspartic or glutamic acid are also inhibitory at 5 X 10(-6) M of amino acid, whereas the monomeric amino acids are inert. Gastric pepsin, a naturally occurring acidic peptide, is inhibitory. Incubation with nonspecific protease reduced the inhibitory effectiveness of normal human urine consistently and significantly, a fact compatible with an important contribution of peptides. A variable additional reduction was produced by subsequent treatment with ribonuclease, suggesting only a small role for polyribonucleotide. Sequential ion exchange and gel filtration chromatography and preparative disc gel electrophoresis yielded inhibitory material enriched with peptides that were strongly acidic and high in proline. Peptides and ribonucleotides seem to contribute to urinary nondialyzable crystal growth inhibitory activity.

Calcium↗

PubMed1979

5'-Hydroxyl polyribonucleotide kinase from HeLa cell nuclei. Purification and properties.

An enzyme, 5'-hydroxyl polyribonucleotide kinase, which catalyzes the phosphorylation of 5'-hydroxyl ends of RNA in the presence of ATP, has been isolated from extracts of HeLa cell nuclei. The kinase requires a divalent cation (Mg2+ or Mn2+) for activity, has an alkaline pH optimum, and is sensitive to the sulfhydryl antagonist N-ethylmaleimide. 5'-hydroxyl terminated polydeoxyribonucleotides are phosphorylated much less efficiently than the 5'-hydroxyl terminated polyribonucleotides, and the kinase preparation is inactive on ribonucleoside 3'-monophosphates. Enzyme activity is inhibited by ADP and by pyrophosphate. The sedimentation coefficient of the kinase is estimated to be 5.6 S from glycerol gradient centrifugation.

Cations, Divalent↗

PubMed1978

Induction by synthetic polyribonucleotide poly(I) of differentiation of cultured mouse myeloid leukemic cells.

The effects of some synthetic polyribonucleotides on induction of differentiation of mouse myeloid leukemic M1 cells were examined. Poly(I) was found to be a potent inducer; on treatment with 100--200 microgram/ml of poly(I) for 2--4 days, M1 cells differentiated into cells resembling macrophages and granulocytes and developed phagocytosis and locomotive activities, Fc receptors and lysozyme activity. Poly(C) was less effective than poly(I) for induction of phagocytic activity, while the other single-stranded RNAs, poly(U) and poly(A), had no effect. Double-stranded RNAs, such as poly(I) . poly(C) and poly(A) . poly(U), were cytotoxic to M1 cells, and differentiation of the cells could not be detected even at the highest tolerable concentrations of these double-stranded RNAs.

Animals↗

PubMed1978

Androgenic regulation of elongation of polyribonucleotide chains on rat ventral-prostate chromatin.

The kinetics of polyribonucleotide-chain elongation by rat ventral-prostate RNA polymerase B with homologous chromatin as a template were investigated. Chain elongation was measured under conditions wherein all initiation had occurred, no reinitiation took place and the reaction rate was constant. The kinetic behaviour of prostate RNA polymerase B was consistent with a mathematical model formulated for the multisubstrate enzyme. The addition of each nucleoside triphosphate was independent of the other three. The overall rate of chain elongation was lower when prostate chromatin from castrated rats was used than with prostate chromatin from normal rats. The inclusion of dihydrotestosterone-receptor complexes stimulated the rate of elongation. Androgenic effects did not appear to be directed towards the addition of individual nucleoside triphosphates, but probably towards one of the other major events in RNA-chain elongation, i.e., unwinding of DNA or movement of the enzyme along the template.

Animals↗

PubMedDate not supplied

[Hydrolysis and the inactivation of double-stranded polyribonucleotides by monkey blood serum].

The effect of Macaca rhesus monkey blood serum on double-stranded polyribonucleotide complexes poly (I).poly (C), poly (G).poly (C), and poly (G,I).poly (C) was studied. The poly (I).poly (C) complex was found to be the most sensitive to hydrolysis as indicated by a decrease of the molecular weight, accumulation of acid-soluble products and a sharp decline of the antiviral and interferon-inducing activities in tissue culture after incubation of the complex in the presence of the serum at 37 degrees C for 1 hour. The poly (G).poly (C) complex was the most stable, and retained its original activity in tissue culture and a high molecular weight after 3-hour incubation with the serum. The interferon-inducing activity of all the complexes under study assayed by intravenous injection in a dose of 2 mg to M. rhesus monkeys was similarly low irrespective of their sensitivity to the serum. Conjectural species features of the interferon induction system in monkeys are discussed.

Animals↗

PubMed1992

[Resistance of natural and synthetic polyribonucleotide inducers of interferon to human blood ribonucleases].

The resistance of polyribonucleotide inductors of interferon to blood ribonucleases was studied. Blood resistance of larifan and ridostin in the free and shielded state as well as that of the complexes of poly(I)-poly(C) and poly(G)-poly(C) were also investigated. A protective action of polylysine against the inductors was detected which, in case it had no effect on the biological activity of the drugs, could provide its recommendation as a compound for shielding the inductors.

Carboxymethylcellulose Sodium↗

PubMed1979

The effect of native and sonicated double-stranded polyribonucleotides on the course of spontaneous autoimmune disease in NZB and NZB/Swiss F1 mice.

The administration of sonicated fractions of f2 phage polyribonucleotides caused an increased weight loss and deterioration of the clinical state in female NZB mice. Discontinuance of the treatment resulted in an improvement of both the clinical state and the genetically determined autoimmune disorders of these mice. Some potential explanations of this effect are discussed.

Animals↗

PubMed1978

Two-component ribonucleotidyl transferase from Escherichia coli. III. Effect of nucleoside diphosphates on synthesis and pyrophosphorolysis of polyribonucleotides by the enzyme.

1. The capacity of two-component ribonucleotidyl transferase to catalyze pyrophosphorolysis of polyribonucleotides is studied. 2. It is shown that nucleoside diphosphates (NDP), not being substrates for the enzyme, activate both the synthesis and pyrophosphorolysis of polynucleotides by the enzyme. The concentration of NDP is important for this effect: with an increase of NDP concentration the rate of synthesis increases and reaches a plateau at 10(-5) M NDP, while the rate of pyrophosphorolysis, attaining maximal values at 10(-5)--10(-3) M NDP, decreases with a further increase of NDP concentration. 3. The possible biological role of two-component ribonucleotidyl transferase is discussed.

Diphosphates↗

PubMed1975

Binding kinetics of mercury(II) TO POLYRIBONUCLEOTIDES.

Kinetic studies of the interaction of Hg(II) with polyribonucleotides have been used to investigate structural fluctuations of the bases in nucleic acids. The reaction of Hg(II) with poly(A)-poly(U) occurs in two phases which differ in time scale by a factor of about 100. The slow phase is first order and exhibits cooperativity or autocatalytic kinetics. The rate is found to increase as decreasing chain length of poly(U) is used to make the double helical complex. The reaction appears to initiate at the ends of poly(U) strands and may be associated with a molecular rearrangement which results in strand separation with Hg(II) being linked only to uridine. The fast reaction phase is second order ans shows little cooperative behavior. Protons are released at this stage indicating alteration of the double helix. The measured second-order rate constant is nearly three orders of magnitude smaller than that found for poly(U) alone. This rate difference suggests that the reactive sites are blocked by double helix formation, and become available for reaction with Hg(II) only through a structural fluctuation. The ratio of rate constants for the reaction of Hg(II) with poly(U) and poly(A)-poly(U) was used to place an upper limit on the equilibrium constant for the structural fluctuation of 2 times 10- minus 3 at 15 degrees and 0.5 M NaClO4. The heat of the "breathing" reaction can be estimated to be similar to 9 kcal/mol from comparison of the temperature coefficient of the reaction with poly(U) to that with poly(A)-poly(U).

Adenine Nucleotides↗

PubMed1975

Structural features of double-stranded polyribonucleotides required for immunological specificity and interferon induction.

Purified antibody to poly(adenylic acid)-poly(uridylic acid) was used in quantitative microcomplement fixation assays to detect conformational variations among several double-helical polyribonucleotide analogs of poly(adenylic acid)-poly(uridylic acid) or poly(inosinic acid)-poly(cytidylic acid) that had been previously evaluated for their ability to induce interferon. Modification at the furanose 2'-position of one or both strands resulted in a dramatic decrease in serological reactivity. Most modifications of the bases caused smaller serological changes, and no base modification caused complete loss of reactivity. The reaction patterns support the conclusion that the structure of the furanose and the overall conformation of the helix are critical in the formation of antigenic determinants. The backbones of both strands appear to be involved in forming a single antigenic site, and base modifications may alter the steric relationship between the backbones. In addition, the same structural changes that substantially alter recognition by antibody also lead to large changes in the interferon-inducing ability of the nucleic acid.

Antigen-Antibody Reactions↗

PubMed1975

Inhibitory effect of synthetic polyribonucleotides on the primary in vitro immune response.

The synthetic double-stranded polyribonucleotides, poly (rA):poly (rU) and poly (rI):poly (rC), were shown to be potent inhibitors of the in vitro plaque-forming cell (PFC) response to a thymus-dependent (SRBC) and thymus-independent (E. coli 0127 LPS) antigen in mouse C57BL/6 spleen cell cultures. The same polynucleotides had no effect on the PFC response of nude (athymic) mouse spleen cells to E. coli 0127 LPS, suggesting that functional T lymphocytes are necessary for the inhibitory effect. Enhancement effects were modest and inconsistent in the cultures. Poly (rA) and poly (rU) were ineffective as inhibitors. The data indirectly suggest that the inhibition may be due to the early production of interferon by functional T lymphocytes.

Animals↗

PubMedDate not supplied

[Compact form of DNA in solution. XII. Double-stranded polyribonucleotide compacting in the presence of polyethylene glycol].

Double-stranded polyribonucleotides (a replicative form of phage f2 RNA--dsRNA and poly(A) poly(U), can adopt a compact from in solutions, containing NaCl and poly(ethylene glycol) (PEG). According to electron-microscopic observations dsRNA compact particles have the form of disks or doughnuts 200--400 A in diameter. X-ray diffraction patterns from dense slurries of dsRNA compact particles show a reflection at a spacing of 35 A, which is indicative of the existance of ordered regions in compact particles. The intense positive CD band, which is characteristic of dsRNA and poly(A) poly(U) compact particles, presumably results from the ordered regions in the particles. Heating of the solution leads to the disappearance of the intense positive CD band, probably as a result of the destruction of the ordered structure of compact particles. Heat or acid denatured dsRNA molecules as well as single-stranded molecules of ribosomal RNA also form large particles in PEG-containing solutions. However, X-ray diffraction patterns from these particles do not show the 35 A reflection and the specific positive band is not present in their CD spectra, which indicates that such particles lack ordered internal structure. It is suggested that similar mechanism of compactization of double-stranded polynucleotides (DNA and RNA) exist, and compact particles may be divided into two families (psi+ and psi-), differing by the secondary structure of double-stranded polynucleotides, which form the particles.

Bacteriophages↗

PubMed1976

Combined enzymatic and chemical approaches to the synthesis of unique polyribonucleotides.

The enzymatic polymerization by polynucleotide phosphorylase of 6-chloro-9-(beta-D-ribofuranosyl)purine 5'-diphosphate to poly(6-chloropurinylic acid) and its conversion to poly(6-thioninosinic acid) is described. The sulfur isostere of poly(I) was found not to form a complex with poly(C), but to form a self-association complex with a Tm around 295 degrees K. The sedimentation velocities, pKa and Tm values of the polymer have been examined under various conditions. A two (or more) stranded helical array is suggested as the most probable structure. Thermal loss of the thione chromophore was noted for poly- (S6I), S6IMP and S6I; the degradation product from S6I was shown to be inosine.

Alkaline Phosphatase↗

PubMed1977

Polyribonucleotides containing thiopurines. Synthesis and properties of poly(1-methyl-6-thioguanylic acid).

The synthesis of 1-methyl-6-thioguanosine 5'-diphosphate and its conversion to poly(1-methyl-6-thioguanylic acid) by means of polynucleotide phosphorylase are described. The polymer exhibited cooperative behavior (Tm = 294 K in the absence of added NaCl) characteristic of a highly stacked single-stranded helical array. In a high salt environment (0.5 M NaCl) the melting was much less cooperative and gave a higher Tm (313 K); this is suggestive of interstrand aggregation involving hydrogen bonding. The polynucleotide exhibited a remarkably high pKa (6.2) compared to that of the mononucleotide (2.6), and formed a very stable acid structure (Tm = 356 K in 50% ethylene glycol). Comparisons with poly(1-methyl-6-thioinosinic acid) and poly(6-thioguanylic acid) establish that both the 2-amino group and the 1-methyl group are required for the formation of the stable acid structure.

Alkaline Phosphatase↗