Résumé
Novos ribonucleosídeos derivados dos sistemas dipirazolo-piridina foram preparados e avaliados quanto à atividade polimerásica das enzimas transcriptase reversa (RT) do vírus HIV-1 e das DNA polimerases humanas alfa e epsilon. Os derivados 1b e 1d inibiram a atividade da transcriptase reversa em concentraçöes de micromolares. Entretanto, as mesmas substâncias näo foram capazes de inibir a atividade polimerase das enzimas DNA-polimerase humana alfa e epsilon.
Sujets)
DNA polymerase II/antagonistes et inhibiteurs , DNA polymerase I/antagonistes et inhibiteurs , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/enzymologie , Pyrazoles/pharmacologie , Pyridines/pharmacologie , Inhibiteurs de la transcriptase inverse , Ribonucléosides/pharmacologieRésumé
It is known that vaccinia core proteins are released into the supernatant fraction when cores are incubated under appropriate conditions. When prepared in the absence of viral transcription this fraction inhibits in vitro protein synthesis. We show here that after incubation, the cores loose the capability to inhibit protein synthesis. Furthermore, we show that no inhibition of translation is observed with supernatant fractions prepared from transcribing cores. SDS-PAGE analysis of the supernatantt fraction of cores obtained in the presence and absence of viral transcription indicated that their protein composiition is similar and approximately 17 peptides are released from the cores and that 4 are phosphorylated. We conclude that the proteins associated with vaccinia cores and released in the presence of ribonucleotides are not involved in protein synthesis inhibition
Sujets)
Techniques in vitro , Inhibiteurs de la synthèse protéique , Transcription génétique , Virus de la vaccine , Protéines , RibonucléotidesRésumé
When a rabbit reticulocyte lysate is incubated in the presence of vaccina cores, protein synthesis is umpaired at the level of the initiation step and the polyribosomes are depolymerized. However, when the same system is coupled with virus transcription: a) protein synthesis is restored, b) the initiation step is not inhibited, and c) the polyribosomes are not disaggregated. A viral factor activated in the absence of virus transcription and not activated when RNA synthesis occurs may be involved in the early mechanism of protein synthesis inhibition by vaccinia virus