Disease relevance of NSC107179

• Splicing of newly formed nuclear RNA transcripts has been demonstrated during adenovirus type 2 (Ad2) mRNA formation in HeLa cells in the presence of "cordycepin," 3' deoxyadenosine, a drug that stops poly(A) addition to nuclear RNA [1].
• We now report that the formation of the 40S--Met-tRNAfMet initiation complex is inhibited in cytoplasmic extracts derived from vaccinia virus-infected cells exposed to cordycepin to block viral gene expression [2].
• In contrast to NGF-mediated neurite outgrowth, the DCC-mediated response was inhibited by treatment with pertussis toxin or the combination of N- and L-type calcium channel blockers, and was unaffected by the transcriptional inhibitor cordycepin [3].
• EHNA (10 micron) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3'-deoxyadenosine) against HeLa cells and against the production of HSV in those cells [4].
• These cordycepin analogues of 2-5A also inhibited partially purified HIV-1 reverse transcriptase [5].

Psychiatry related information on NSC107179

• To test the hypothesis that testosterone stimulates masculine social behaviors by inducing transcription of messenger ribonucleic acid (mRNA), we studied the effects of cordycepin, an adenosine analog that preferentially impairs synthesis of polyadenylated mRNA [6].

High impact information on NSC107179

• The response of differentiating MEL cells to the nucleotide analogue cordycepin reveals a previously unrecognized aspect of the molecular events which cause commitment of these cells to terminal erythroid differentiation [7].
• The effects of cordycepin (3'-deoxyadenosine) on the metabolism of TAT and its mRNA are also complex, but differ in several respects from those of AMD [8].
• Stimulation of in vitro translation of messenger RNA by actinomycin D and cordycepin [9].
• Actinomycin D and cordycepin were tested for their effect on translation in the wheat germ embryo extract and reticulocyte lysate assays for in vitro protein synthesis [9].
• We conclude that the poly(A) removing activity is a 3' exonuclease since (i) reaction intermediates gradually lose the poly(A) tail, (ii) degradation is prevented by the presence of a cordycepin residue at the 3' end and (iii) RNAs having internally located poly(A) stretches are poor substrates for degradation [10].

Chemical compound and disease context of NSC107179

• The stimulation of [3H]dGlu uptake induced by Sindbis virus was insensitive to the drug actinomycin D, but was blocked by cordycepin [11].
• This metabolic conversion provides a mechanism for the parasite-selective toxicity of 3'-deoxyinosine: Leishmania can aminate the 6-position of 3'-deoxyinosine residue, thereby converting a less toxic nucleoside into the cordycepin nucleotides that are known to be highly toxic to cells [12].

Biological context of NSC107179

• Cordycepin, which inhibits polyadenylation but not mRNA synthesis, has no such effect [13].
• A cordycepin "chase" experiment yielded half-life values for the messenger RNA species which were, in general, larger by a factor of 1.5 to 2.5 than those estimated in the labeling kinetics experiments [14].
• These results suggest that cordycepin triphosphate, and perhaps cordycepin too, may affect transcription via interference with the phosphorylation of non-histone chromosomal proteins [15].
• Inhibition of nucleic acid methylation by cordycepin. In vivo synthesis of S-3'-DEOXYADENOSYLMETHIONINE BY WI-L2 human lymphoblasts [16].
• Preliminary evidence suggests that this effect was not dependent upon a stimulation of protein synthesis, but the observed stimulation and inhibition of control rates of gluconeogenesis by cycloheximide and cordycepin, respectively, demonstrate the difficulties of working with such inhibitors in attempting to answer this question [17].

Anatomical context of NSC107179

• Whereas the naturally occurring core (2'-5')oligo(A) was cytotoxic to uninfected lymphocytes and proliferating lymphoblasts, the core cordycepin analog was not [18].
• In contrast, inhibitors of RNA synthesis (cordycepin or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) enhanced the survival of etoposide-treated HL-60 cells as much as 20-fold [19].
• Furthermore, cordycepin and actinomycin D are without effect on polyribosomes indicating that colchicine is not simply inhibiting the production or transport of new mRNA [20].
• The present studies report that 2',5'-An and its cordycepin analog also augmented the tumoricidal activity of human NK cells [21].
• The possibility that mRNAs coding for these 11 cordycepin-insensitive heat-shock proteins would be found in non-heat-shocked thymus cells was investigated [22].

Associations of NSC107179 with other chemical compounds

• Replacement of the 3' hydroxyl group of the adenosine moieties of 2-5A with hydrogen atoms (i.e., cordycepin analogues of 2-5A) converted authentic 2-5A trimer into anti-HIV-1 agents in vitro [5].
• Cleavage, but not polyadenylation, occurred in the presence of EDTA or when ATP was replaced with 3' dATP (cordycepin) or AMP(CH2)PP, a nonhydrolyzable analog of ATP [23].
• The effect of the adenosine deaminase inhibitor, 2'-deoxycoformycin, on the inhibitory effect of cordycepin on nuclear RNA synthesis was examined in L1210 cells in vitro [24].
• Potentiation by 2'-deoxycoformycin of the inhibitory effect by 3'-deoxyadenosine (cordycepin) on nuclear RNA synthesis in L1210 cells in vitro [24].
• Cordycepin and cordycepin triphosphate competitively inhibited phosphorylation of urea-soluble nuclear proteins with a Ki of 1.2 X 10(-3) and 8 X 10(-5) M, respectively [15].

Gene context of NSC107179

• Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells [25].
• Anti-interleukin-10 neutralizing antibody could not completely block the suppressive effect of cordycepin on production of interleukin-2 [25].
• Sequencing using cordycepin triphosphate to terminate (-) strands during their synthesis by the replicase generated sequence ladders that confirmed that copying was accurate, and that initiation occurred very close to the 3' end [26].
• In addition to culture density, removal of extracellular calcium or sodium during irradiation, treatment with amiloride, or inhibition of new mRNA synthesis with cordycepin was shown to influence the UVR-induced alteration in release of IL-3 or GM-CSF bioactivity from both confluent and subconfluent PAM 212 cells [27].
• Actually, the addition of cordycepin during initial incubation with IFN increased the subsequent response to IFN-gamma (and also to RA and 1,25[OH]2D3) [28].

Analytical, diagnostic and therapeutic context of NSC107179

• Uptake studies of the 2',5'A3 and 2',5'-3'dA3 cores, using high-pressure liquid chromatography, demonstrated that both cores were rapidly degraded in the tissue culture medium and taken up as adenosine or cordycepin, respectively [29].
• Of these, only 3'-deoxyadenosine (cordycepin) had similar HPLC characteristics [30].
• We now report that the inhibitory effect of cordycepin results in a reduction of the number of cells producing virus as measured by the infectious center assay and fluorescent antibody technique [31].
• Biochemical studies (incorporation of radioactive stracers into NRA, affinity chromatography on poly U-Sepharose) carried out in parallel with and under conditions comparable to those used in electron microscopy show that cordycepin does not greatly affect the increase in ribosomal RNA observed under the effect of estradiol [32].
• The decay in translatable glucokinase mRNA, as determined after administration of cordycepin, was identical in the hypothyroid and euthyroid fed state, while adrenalectomy resulted in a significant decrease in the specific mRNA half-life [33].

References