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Biomedical subjects

J Pitha

Publications and source records attributed to J Pitha.

At least 145 records · Page 8Linked to original sources
PubMed1977

Uptake and fate of water-soluble, nondegradable polymers with antiviral activity in cells and animals.

Poly(9-vinyladenine) and poly(1-vinyluracil) which are nondegradable, soluble polymers are taken up partially by mammalian cells grown in culture. The polymers remain associated with cells for several generations. In mice, after ip application, polymers slowly accumulate in liver, spleen, and thymus and remain there for as long as a month. Thus, these polymers which suppress the replication of murine leukemia viruses also accumulate in organs where the virus replicates. However, their antiviral activity does not reflect the amount of polymer found in these animal tissues. We propose that the polymers are gradually segregated into a group of cells or into subcellular organelles away from primary sites of virus replication. The results suggest that for a directly acting polymeric drug, a half-life over 24 h is without advantage.

Adenine↗
PubMed1976

Ionophorous polymers. Interaction with polynucleotides and effects on RNA-directed DNA polymerase activity.

Poly(vinylbenzo-18-crown-6), a water-soluble polymer endowed with ion-binding crown moieties as pendent groups, forms insoluble complexes with polyadenylate in the presence of K+; the corresponding monomeric benzo-18-crown-6, does not form a precipitate under the same conditions. In the presence of Na+ and Mn2+ which in aqueous solution complex weakly to crown compounds, no coprecipitation of the crown polymer and polyadenylate occurs; nevertheless, the crown polymer strongly binds to immobilized polyadenylate even under these conditions. The interactions of crown polymer with the poly-nucleotide result in a loss of templating ability of the latter. Using RNA-dependent DNA polymerase of murine leukemia virus it was found that (1) enzymatic action is efficiently inhibited even in the absence of ions which coprecipitate crown polymer and template, (2) inhibition is reversed by addition of excess polynucleotide and (3) monomeric crown does not inhibit the reaction.

Binding Sites↗
PubMed1976

Template specific inhibitor of mammalian DNA polymerases.

A study of the inhibition of mouse cellular DNA polymerases by poly-nucleotides and their vinyl analogs is presented. Poly(dT)-directed poly(dA) synthesis by representatives of all three classes of cellular DNA polymerase could be completely inhibited by poly(9-vinyladenine), although higher concentrations were required in the case of the gamma class enzyme. Studies on the mechanism of the inhibition using the alpha class DNA polymerase and different templates showed that the enzyme activity was inhibited in all cases where base-pairing between the vinyl polymer and the template occurred; poly(9-vinyladenine) did not interfere with the replication of templates to which it does not bind. The inhibition occurred shortly after addition of poly(9-vinyladenine) to ongoing reactions, yet the enzyme was not displaced from the template - primer complex.

Animals↗
PubMed1976

Effects of Poly(1-vinyluracil) and Poly(9-vinyladenine) on viral RNA-directed DNA polymerase.

The effects of poly(1-vinyluracil) [poly(vU)] and poly(9-vinyladenine) [poly(vA)] on the RNA-dependent DNA polymerase activity of murine leukemia virus (Moloney strain) were studied. Vinyl polymers themselves cannot act as templates for the polymerase. However, if a vinyl polymer is added to a polymerase reaction mixture in which a complementary polynucleotide serves as the template, the reaction is inhibited: thus with polyribocytidylic acid as template and oligodeoxyguanylic acid as primer, neither poly(vU) nor poly(vA) had a significant effect; when polyribouridylic acid was used as template and oligodeoxyadenylic acid as primer, poly(vA) inhibited polymerase activity while poly(vU) had little effect; when polyriboadenylic acid was a template and oligodeoxy thymidylic acid was a primer, poly(vU) was an inhibitor. Complex effects were noted with the latter system and poly(vA); either stimulation or inhibition of the reaction was observed, depending on the concentration of poly(vA). The stimulation brings about a decrease in the amount of lower-molecular-weight materials in the product and is caused by the interaction of poly(vA) with the template-primer. Thus vinyl polymers differ from polynucleotides in their mechanism of inhibition of viral polymerase, since the latter inhibit the enzyme by binding to it.

Adenine↗
PubMed1975

Hydrogen bonding abilities of 2,4-dithiouridine derivatives.

The base pairing ability of a di-2,4-thiouridine derivative was studied in carbon tetrachloride solutions by the methods of infrared spectroscopy. The strength of the association by hydrogen bonding was found to decrease in the following order: adenine-uracil, adenine-di-2,4-thiouracil, uracil-uracil, and di-2,4-thiouracil-di-2,4-thiouracil. These findings contrast with the previously demonstrated fact that poly(s2s4U) is strongly self-associated and does not form a complex with poly(A). To correlate these results, it is proposed that long range stabilizing forces are acting between the di-2,4-thiouracil residues in polynucleotide chains. This assumption also explains the existence of an ordered structure in the alternating copolymer poly(s2s4U-A).

Adenine Nucleotides↗
PubMed1973

Inhibition of murine leukemia virus replication by poly(vinyluracil) and poly(vinyladenine).

Poly(1-vinyluracil) and poly(9-vinyladenine), as well as the corresponding polynucleotides poly(uridylate) and poly(adenylate), inhibit acute murine leukemia virus infection in mouse-embryo cells, but they do not significantly inhibit the replication of Sindbis and vesicular stomatitis viruses. The polymers were most effective as inhibitors when added during an early stage of virus replication. Effects of vinyl polymers on the RNA-dependent DNA polymerase from the virions of murine leukemia virus were also observed.

Adenine Nucleotides↗