Disease relevance of CCRIS 3233

• Transfer RNAs terminating 2'-or 3'-deoxyadenosine were prepared from unfractionated E. coli and yeast (Saccharomyces cerevisiae) tRNAs and purified to remove unmodified tRNAs [1].
• Labeled adenovirus type 2 nuclear RNA molecules from cells treated with 3'-deoxyadenosine (3'dA) were earlier reported to lack polyadenylic acid [poly(A)], but to be correctly spliced in the nucleus (M. Zeevi et al., Cell 26:39-46, 1981) [2].
• Influenza virus RNA's in the cytoplasm of chicken embryo cells treated with 3'-deoxyadenosine [3].
• Studies on the mechanism of cytotoxicity of 3'-deoxyadenosine N1-oxide in different strains of Ehrlich ascites tumor cells [4].
• Cordycepin (3'-deoxyadenosine), which is known to inhibit the repair of potentially lethal damage in irradiated cells, induced mutations in both Salmonella and soybean test systems [5].

High impact information on CCRIS 3233

• The crystal structure of the PAP from Saccharomyces cerevisiae (Pap1) has been solved to 2.6 angstroms, both alone and in complex with 3'-deoxyadenosine triphosphate (3'-dATP) [6].
• The 50-base cis element directs polyadenylation, but not translation per se, as a transcript that terminates with 3'-deoxyadenosine (cordycepin) is not recruited for translation [7].
• Recent suggestions that elongation factor Tu (EF-Tu) is specific for 2'-O-aminoacyl-tRNA, as compared with the 3'-isomer, prompted us to assay [3H]aminoacyl-tRNAs from Escherichia coli terminating in 2'- or 3'-deoxyadenosine for binding to EF-Tu to determine the possible positional specificity of the factor [8].
• The inhibitory effects on cell growth and to some extent on ERalpha were mimicked by 2-chloro-adenosine >3'-deoxyadenosine> adenosine but not by a variety of other ligands [9].
• The DNA cleavage-ligation reaction of DNA topoisomerase I was investigated employing synthetic DNA substrates containing 3'-deoxyadenosine or 3'-deoxythymidine at specific sites and acceptor oligonucleotides of different lengths [10].

Chemical compound and disease context of CCRIS 3233

• A structural analogue of ATP, 3'-deoxyadenosine triphosphate (3'-dATP), has been synthesized from cordycepin (3'-deoxyadenosine), characterized, and determined to be an inhibitor of ATP-dependent DNA synthesis in Escherichia coli cells which have been reduced permeable to nucleoside triphosphates by treatment with toluene [11].
• The simultaneous administration of 3'-deoxyadenosine N1-oxide (3'-dANO) and the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) or 2'-deoxycoformycin (2'-dCF) to mice bearing Ehrlich ascites tumor cells resistant to 3'-dANO resulted in 80%-90% inhibition of tumor growth in vivo [12].
• The substrate specificity of trypanosomal MeSAdo/Ado phosphorylase differed from that of a mammalian MeSAdo phosphorylase (derived from murine Sarcoma 180 cells) in that it was able to phosphorolyze 2'-deoxyadenosine, 3'-deoxyadenosine and 2',3'-dideoxyadenosine [13].

Biological context of CCRIS 3233

• The positional specificity in the aminoacylation of Escherichia coli tRNAGly by its cognate aminoacyl-tRNA synthetase has been studied using tRNAGlys terminating in 2'- or 3'-deoxyadenosine under conditions believed to alter tRNA conformation [14].
• In addition, late in the cycle (6 to 8) complementary virus-specific RNA's were the predominantly labeled species, suggesting that higher concentrations of 3'-deoxyadenosine selectively inhibit influenza viral genome replication [3].
• The nucleoside analogue cordycepin (3'-deoxyadenosine), when protected against ADA deamination, is specifically cytotoxic for TdT-positive leukemia cells [15].
• With 3'-deoxyadenosine a corresponding effect was obtained although the apparent coupling between phosphorylation of 3'-deoxyadenosine and catabolism of adenine ribonucleotides was not complete [16].
• If the 3'terminal adenosine in these tRNAs is replaced by either 3'-deoxyadenosine or formycin, little if any hydrolysis can be observed [17].

Anatomical context of CCRIS 3233

• The effect of cordycepin (3'-deoxyadenosine) on newly synthesized globin mRNA in cultured mouse fetal liver erythroid cells is investigated [18].
• Cordycepin (3'-deoxyadenosine) was previously shown to inhibit virus production induced by iododeoxyuridine from murine fibroblasts (Wu et al., 1972) [19].
• The possibility that 3'-deoxyadenosine triphosphate inhibits a reaction at the nuclear membrane or nuclear pore complex is considered [20].
• 3'-deoxyadenosine and implantation of delayed blastocysts in mice [21].
• The effect of cordycepin (3'-deoxyadenosine), an inhibitor of messenger RNA synthesis, on the induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase mediated by lipid-depleted serum was studied in isolated human lymphocytes [22].

Associations of CCRIS 3233 with other chemical compounds

• When Swiss 3T3 fibroblasts were used as host cells, allopurinol, 3'-deoxyinosine, 3'-deoxyadenosine, and 3'-azid-3'-deoxythymidine also markedly inhibited T. cruzi proliferation [23].
• All the analogs tested--3'-deoxyguanosine (3'-dG), 3'-deoxyadenosine (3'-dA), and N6-butyryl-3'-deoxyadenosine (N6-BC)--at a dose of 100 mg/kg, enhanced the tumor cell killing by L-PAM as measured by an in vivo/in vitro procedure [24].
• Its formation was greatly stimulated by hypoxanthine and, under conditions where their deamination was not blocked, by adenosine and 2'- and 3'-deoxyadenosine [25].
• The nucleoside analogue cordycepin (3'-deoxyadenosine, 3'-dA) is substantially more cytotoxic to terminal deoxynucleotidyl transferase positive (TdT+) leukemic cells than to TdT leukemic cells in vitro in the presence of an adenosine deaminase inhibitor, deoxycoformycin (dCF), and has been considered as a therapeutic agent for TdT+ leukemia [26].
• Relative ADA activity towards 3'-deoxyadenosine and 6-chloropurine riboside was lower by 30% and 40%, respectively [27].

Gene context of CCRIS 3233

• This cyclin A2 may be generated from maternally recruited cyclin A2 mRNA because its accumulation was inhibited by 3'-deoxyadenosine, which inhibits mRNA polyadenylation [28].
• Synergistic effect of 3'-deoxyadenosine N1-oxide and adenosine deaminase inhibitors on growth of Ehrlich ascites tumor cells in vivo [12].
• Previous studies of the homologous aminoacylations of Escherichia coli and yeast tRNATrp's terminating in 2'- and 3'-deoxyadenosine established that E. coli tryptophanyl-tRNA synthetase activates its cognate tRNA preferentially on the 2' position, while the corresponding yeast enzyme utilizes the 3' position on its homologous substrate tRNA [29].
• Six purified Escherichia coli and yeast tRNA's were converted to positionally defined tRNA's terminating in 2'- and 3'-deoxyadenosine; the modified (amino-acyl) tRNA's were compared for their abilities to bind to elongation factor Tu (EF-Tu) in the presence both of GTP and guanylylimidodiphosphate (GMP-P(NH)P) [30].
• Intracellular inhibition of chromatin binding and transformation of androgen receptor by 3'-deoxyadenosine [31].

Analytical, diagnostic and therapeutic context of CCRIS 3233

• Different regimens of intraperitoneal injections of 3'-deoxyadenosine were applied 3 days after ovariectomy [21].
• The effect of 3'-deoxyadenosine N(1)-oxide on growth in vitro and in vivo on Ehrlich ascites tumor and on a human squamous lung cell carcinoma xenograft in nude mice [32].
• Crystallization of the resulting radioactive 3'-deoxyadenosine to a constant specific activity showed incorporation of both labeled compounds [33].

References