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At least 19 recordsLinked to original sources
PubMed1992

Strand breakage in poly(C), poly(A), single- and double-stranded DNA induced by nanosecond laser excitation at 193 nm.

Single- and double-stranded calf thymus DNA and two polynucleotides (0.4 mM) were studied in aqueous solution at pH approximately 7 using pulsed, 20 ns laser excitation at 193 nm. Monophotonic ionization of the nucleic acids is suggested from the linear dependences of the concentration of ejected electrons and the number of single- and double-strand breaks (ssb, dsb, respectively) on laser intensity (IL) in the range (0.2-3) x 10(6) W cm-2. The quantum yields of formation of hydrated electrons (phi e-) and ssb and dsb (phi ssb and phi dsb) are therefore independent of IL. In contrast, under 248 nm excitation these quantum yields increase linearly with IL under otherwise comparable conditions. Nevertheless, several effects and mechanistic implications are analogous using lambda exc = 193 and 248 nm. For polycytidylic acid, poly(C), in Ar-saturated solution for example, the efficiency of ssb per radical cation (eta RC = phi ssb/phi e-) is similar to the efficiency of ssb per OH radical (eta OH). For polyadenylic acid, poly(A), and single- and double-stranded DNA eta RC (lambda exc = 193 nm) is significantly smaller than eta OH. The ratio phi ssb (N2O)/phi ssb (Ar) is approximately 2 for poly(C), approximately 4 for poly(A) approximately 10 for DNA; the conversion of hydrated electrons into OH radicals in N2O-saturated solution and smaller eta RC than eta OH values in the case of DNA account for these results. For double-stranded DNA phi dsb does not depend on IL but increases linearly with the dose, indicating an accumulative effect of two ssb to generate one dsb. The critical distance for this event is 60-85 phosphoric acid diester bonds.

Animals↗
PubMedDate not supplied

[Comparative study of the toxicity of poly G-poly C and poly I-poly C in different objects].

The poly(G).poly(C) complex has the same interferon-inducing and antiviral activity upon parenteral administration to white mice as poly(I).poly(C), but is considerably less toxic. Upon intravenous inoculation of poly(I).poly(C) to mice its LD50 is 15.8 mg/kg whereas poly(G).poly(C) is not toxic in doses up to 200 mg/kg. In rabbits inoculated with poly(I).ploy(C) intravenously its LD50 is 0.22 mg/kg, while poly(G).poly(C) is not toxic in doses of 1 mg/kg. Histological examinations of different organs of mice and rats revealed no pathomorphological changes after a single intravenous and intraperitoneal inoculation of poly(G).poly(C). It exerted no embryotoxic effect in mice in a dose of 5 mg/kg and was considerably less toxic than poly(I).poly(C) in continuous diploid cell cultures of human embryo lung cells.

Animals↗
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↗
PubMedDate not supplied

[Study of poly(C) and poly(I)-poly(C) complexes with model phospholipid membranes by infrared spectroscopy].

The temperature dependence of poly(C) is shown by the infrared spectroscopy to be different for the free polynucleotide and for the polynucleotide in complexes with membranes. The intensity of stretching vibrations of C = 0 bond of poly(C) in the complex appears to be sensitive to the temperature. The intensity of this band is sharply decreased by increasing the temperature. This effect depends upon concentration of Mg2+-cations. Adsorption of poly(I)-poly(C) on the surface of vesicles from phosphatidylcholine results in the increase of the double helix.

Hot Temperature↗
PubMed1990

8-Azido double-stranded RNA photoaffinity probes. Enzymatic synthesis, characterization, and biological properties of poly(I,8-azidoI).poly(C) and poly(I,8-azidoI).poly(C12U) with 2',5'-oligoadenylate synthetase and protein kinase.

The technique of photoaffinity labeling has been applied to the double-stranded RNA (dsRNA)-dependent enzyme 2',5'-oligoadenylate (2-5A) synthetase to provide a means for the examination of RNA-protein interaction(s) in the dsRNA allosteric binding domain of this enzyme. The synthesis, characterization, and biological properties of the photoaffinity probe poly[( 32P]I,8-azidoI).poly(C) and its mismatched analog poly[( 32P]I,8-azidoI).poly(C12U), which mimic the parent molecules poly(I).poly(C) and poly(I).poly(C12U), are described. The efficacy of poly[( 32P]I,8-azidoI).poly(C) and poly[( 32P]I,8-azidoI).poly(C12U) as allosteric site-directed activators is demonstrated using highly purified 2-5A synthetase from rabbit reticulocyte lysates and from extracts of interferon-treated HeLa cells. The dsRNA photoprobes activate these two 2-5A synthetases. Saturation of 2-5A synthetase is observed at 6 x 10(-4) g/ml poly[( 32P]I,8-azidoI).poly(C) following photolysis for 20 s at 0 degrees C. The photoincorporation of poly[( 32P]I,8-azidoI).poly(C) is specific, as demonstrated by the prevention of photoincorporation by native poly(I).poly(C). DNA, poly(I), and poly(C) are not competitors of poly[( 32P]I,8-azidoI).poly(C). Following UV irradiation of 2-5A synthetase with poly[( 32P]I,8-azidoI).poly(C), the reaction mixture is treated with micrococcal nuclease to hydrolyze azido dsRNA that is not cross-linked to the enzyme. A radioactive band of 110 kDa (the same as that reported for native rabbit reticulocyte lysate 2-5A synthetase) is observed following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The specific photolabeling of the 2-5A synthetase suggests that the azido dsRNA is intrinsic to the allosteric binding domain. The utility of poly[( 32P]I,8-azidoI).poly(C) for the detection of dsRNA-dependent binding proteins and the isolation of peptides at or near the allosteric binding site is discussed.

2',5'-Oligoadenylate Synthetase↗
PubMed1975

[A calorimetric study of the triple helix formation: interaction of poly(C) - guanosine - protonated poly(C)].

The triple helix formation of poly(C) - guanosine - poly(C+) was investigated by the help of an LKB scanning micro-calorimeter. The existence of the triple helix could also be shown by recording the melting curves. The ultraviolet absorption at different wave lengths namely 275 nm, 260 nm, and 245 nm was plotted as a function of the temperature. Furthermore formation of the triple helix was shown by plotting the ultraviolet absorption at 245 nm during the increasing addition of guanosine solution to a fixed amount of poly(C) in the solution. Finally the formation of the triple helix was demonstrated by plotting the ultraviolet absorption at 245 nm of a certain mixture of the components while the pH value of the solution was continuously lowered. All these methods show that the monomer interacts with the polymer double helix to form a triple helix. The calorimetric measurements show that the reaction enthalpy is concentration dependent. Above a threshold concentration a rapid increase of the reaction enthalpy is observed. This increase occurs in a very narrow concentration interval. Above this interval a final value of the reaction enthalpy is reached. The amount of the reaction enthalpy for the interaction of guanosine with poly(C) - poly(C+) double helix is 5.5 Kcal (mol base triplet)-1.

Calorimetry↗
PubMed1987

Stimulation of collagenase production in human synovial fibroblast cultures by poly (I). poly (C).

Poly (I). poly (C) was found to induce collagenase secretion in both "normal" and "rheumatoid" synovial fibroblast cultures. Induction was time dependent, was maximal at 20-50 micrograms/ml poly (I). poly (C) and was dependent on de novo synthesis. Induction was prevented by hydrocortisone (0.1 microgram/ml) but inhibition of prostaglandin E production by diclofenac (0.2 microgram/ml) or ibuprofen (0.1 microgram/ml) did not affect collagenase production. Collagenase induction was accompanied by stimulation of hyaluronic acid and prostaglandin E production. This in vitro system may represent a model for the study of pathological secretory activities in the inflamed joint.

Cell Line↗
PubMed1971

Dose responsiveness and variation among inbred strains of mice in production of interferon after treatment with poly (I)-poly (C) (poly-D-lysine) complexes.

Poly-d-lysine forms a stochiometric complex with poly(I) . poly(C) which has a higher T(m) (83 C in 0.15 m NaCl) than the uncomplexed double-stranded polyribo-nucleotide (63 C). The complex was superior to poly(I) . poly(C) alone as an interferon inducer in vivo. Significant serum interferon titers were attained in Swiss mice during a 24-hr period after intraperitoneal injection of 10 to 300 mug of poly(I) . poly(C) [1.0 poly-d-lysine] complex, at concentrations of 100 to 1,000 mug/ml. The serum interferon responses (average and maximum titers) of a series of inbred strains of mice to a single intraperitoneal injection of 100 mug of complex decreased in the order: Swiss > DBA/2 > C3H > BALB/c > CF-1 > AKR, C57Bl/6, NZB > SJL > NZW and varied by a factor of approximately 100 from the most to the least responsive.

Animals↗
PubMed1985

Oligomerization of activated derivatives of 3'-amino-3'-deoxyguanosine on poly(C) and poly(dC) templates.

3'-amino-3'-deoxyuridine reacts with the nucleoside 5'-phosphorimidazolides in aqueous solution to give dinucleoside phosphoramidates. The reactions are one to two orders of magnitude faster than the corresponding reactions of uridine. In the presence of poly(C) or poly(dC) it is known that guanosine-5'-phosphorimidazolide does not condense efficiently or regiospecifically. However, the introduction of a methyl group at the 2-position of the imidazole ring leads to efficient synthesis of long 3'-5'-linked oligomers. The corresponding imidazole derivatives of 3'-amino-3'-deoxyguanosine-5'-phosphate both condense on these templates to give virtually identical families of products. Our results suggest that the intrinsically greater nucleophilicity of the amine groups will permit a much wider range of efficient template-directed syntheses with 3'-amino-3'-deoxynucleoside derivatives than with the corresponding derivatives of the parent nucleosides.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

[Effect of synthetic polynucleotides and RNA on poly(C)-dependent poly(G) polymerase activity of Q beta replicase].

The effect of synthetic polynucleotides and phage RNA on poly(C)-dependent synthesis of poly (G) by Qbeta replicase is studied. It is shown that single stranded poly(U) and poly (dT) are strong inhibitors whereas structured polynucleotides poly(A), MS2 RNA as well as double stranded complexes poly(A)-poly(U) and poly(A)-poly(dT) do not affect the synthesis of poly(G). It is suggested that contact region of template with enzyme has single stranded unhelical structure and affinity of polynucleotides to Qbeta replicase is determined by degree of their secondary structure.

Kinetics↗
PubMedDate not supplied

[Study of the intermolecular association of poly(G).poly(c) and poly(dG).poly(dC) in solutions by methods of 1H to 3H exchange and electron microscopy].

The kinetic of 1H leads to 3H exchange between water and C(8)H-groups of the guanylic residues in poly(G) . poly(C) and poly(dG) . poly(dC) was investigated within the temperature range from 30 to 90 degrees in 0.5 M NaCl (pH 7.2). It was shown that the exchange in freshly dissolved preparations at temperatures lower than 50 degrees proceeds faster than that in the case of GMP. According to the ylide mechanism of the exchange reaction the observed acceleration of the exchange is considered as a consequence of associates formation in poly(G) . poly(c) and poly(dG) . poly(dC) solutions at temperatures lower than 50 degrees. Associates are stabilized by intermolecular hydrogen bonds in which N(7) atoms of guanylic residues take part. The increase of the temperature is accompanied by gradual disappearance of the exchange acceleration. The retardation of exchange, which is characteristic of most non-associated double-stranded polynucleotides and nucleic acids is observed at the temperatures above 60 degrees. The retardation points to thermal destruction of the associates at temperatures higher than 50 degrees. The associates which are characterized by ordered structure including several "side by side" arranged double-stranded molecules were observed by electron microscopy. The addition of EDTA to solutions as well as the increase of temperature leads to destruction of the associates whereas the addition of Mg2+ makes the associates more stable.

Chemical Phenomena↗
PubMedDate not supplied

[Influence of a complex of poly(I). poly(C) and poly-l-lysine on the course of vaccinia in monkeys].

Experiments of 22 Macaca rhesus monkeys were carried out to study the interferon-inducing and antiviral activity of poly(I) - poly(C) and of its complex with poly-l-lysine. The complexed double-stranded polyribonucleotide induced active production of serum interferon and markedly protected the monkeys inoculated intradermally with vaccinia virus (10 monkey ID50 by intradermal inoculation). The effectiveness of the protective effect depended on the schedule and routes of administration of the preparation. The greatest prophylactic and therapeutic effect was achieved by local administration of the complex in a dose of 1 mg/1 kg of body weight. This also prolonged the incubation period by 2-3 times and reduced the duration of persistence of skin lesions approximately by half. By the intravenous route, the best protection was achieved by 2 injections of 2 mg/kg at an interval of 96 hours. Four daily injections of the complex exerted virtually no effect on the course of vaccinia infection. The animals receiving the complexed poly(I) - poly(C) developed virus-neutralizing antibody to the same titres as control animals and were resistant to reinfection with vaccinia virus. A second injection of the complexed poly(I)-poly(C) 96 hours after the primary inoculation induced the same interferon production as the initial administration of the preparation. The monkeys inoculated intravenously with 2 mg/kg poly(I) - poly(C) showed no interferon in their blood serum and were also poorly protected against vaccinia virus infection.

Animals↗
PubMedDate not supplied

[Dependence of the antiviral activity of the poly(G).poly(C) complex on the size of the continuous poly(C)segments].

Modification of poly(C) by various frequency treatment with adenosine non-complementary to guanosine has produced poly(G) X poly (C.A) complexes with continuous double-stranded areas the length of which is determined by C/A ratio. Studies of the antiviral activity of poly(G).poly(C,A) complexes with C/A from 10:1 to 90:1 and poly(G).poly(C) in vesicular stomatitis virus-infected chick embryo cell cultures and in experimental tick-borne encephalitis of mice demonstrated that the maximum activity is achieved at an average lengths of double-stranded areas of 90 nucleotide pairs. At the same time, a low but statistically significant antiviral activity is observed at a length of double-stranded areas of 10-30 nucleotide pairs.

Animals↗