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Mutation Research Aug 1994DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate... (Review)
Review
International Commission for Protection Against Environmental Mutagens and Carcinogens. Deoxyribonucleoside triphosphate levels: a critical factor in the maintenance of genetic stability.
DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate that the control of DNA precursor concentrations is essential for the maintenance of genetic stability, and suggest that factors which offset this control may contribute to environmental mutagenesis and carcinogenesis. In this article, we review the biochemical and genetic mechanisms responsible for regulating the production and relative amounts of intracellular DNA precursors, describe the many outcomes of perturbations in DNA precursor levels, and discuss implications of such imbalances for sensitivity to DNA-damaging agents, population monitoring, and human diseases.
Topics: Animals; Bacteria; Cell Cycle; DNA Damage; DNA Replication; Deoxyribonucleosides; Deoxyribonucleotides; Fungi; Homeostasis; Humans; Mutation; Postural Balance
PubMed: 7519315
DOI: 10.1016/0165-1110(94)90006-x -
Current Protocols in Nucleic Acid... Jul 20057-Substituted 7-deazapurine (pyrrolo[2,3-d]pyrimidine) 2'-deoxyribonucleosides are synthesized by stereoselective nucleobase anion glycosylation. The introduction of a...
7-Substituted 7-deazapurine (pyrrolo[2,3-d]pyrimidine) 2'-deoxyribonucleosides are synthesized by stereoselective nucleobase anion glycosylation. The introduction of a halogen at C7 is performed regioselectively either on the nucleobase or on the nucleoside. The pK(a) values of a series of 7-deazapurine 2'-deoxyribonucleosides are provided, and fluorescence properties are also discussed.
Topics: Deoxyribonucleosides; Molecular Structure; Purines; Pyrimidines; Pyrroles; Stereoisomerism
PubMed: 18428932
DOI: 10.1002/0471142700.nc0110s21 -
Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters.Biochemical and Biophysical Research... Jun 2021Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize...
Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize CNT-subtype specificity to understand the systemic disposition of deoxyribonucleosides (dNs) and their analogs, the involvement of CNTs in transporting dNs is not fully understood. In this study, using COS-7 cells that transiently expressed CNT1, CNT2, or CNT3, we investigated if CNTs could transport not only ribonucleosides but also dNs, i.e., 2'-deoxyadenosine (dAdo), 2'-deoxyguanosine (dGuo), and 2'-deoxycytidine (dCyd). The cellular uptake study demonstrated that dAdo and dGuo were taken up by CNT2 but not by CNT1. Although dCyd was taken up by CNT1, no significant uptake was detected in COS-7 cells expressing CNT2. Similarly, these dNs were transported by CNT3. The apparent K values of their uptake were as follows: CNT1, K = 141 μM for dCyd; CNT2, K = 62.4 μM and 54.9 μM for dAdo and dGuo, respectively; CNT3, K = 14.7 μM and 34.4 μM for dGuo and dCyd, respectively. These results demonstrate that CNTs contribute not only to ribonucleoside transport but also to the transport of dNs. Moreover, our data indicated that CNT1 and CNT2 selectively transported pyrimidine and purine dNs, respectively, and CNT3 was shown to transport both pyrimidine and purine dNs.
Topics: Animals; Biological Transport, Active; COS Cells; Chlorocebus aethiops; Deoxyadenosines; Deoxycytidine; Deoxyguanosine; Deoxyribonucleosides; Humans; Kinetics; Membrane Transport Proteins; Recombinant Proteins
PubMed: 33910126
DOI: 10.1016/j.bbrc.2021.04.075 -
Nucleic Acids Research Mar 1998The structure of the deoxyribonucleoside derived from N 6-methoxy-2, 6-diaminopurine (dK) was examined by NMR. The methoxyamino residue was found predominantly in the... (Comparative Study)
Comparative Study
The structure of the deoxyribonucleoside derived from N 6-methoxy-2, 6-diaminopurine (dK) was examined by NMR. The methoxyamino residue was found predominantly in the imino rather than the amino tautomer (ratio: 9:1 in DMSO). The nucleoside proved to be a potent transition mutagen in Escherichia coli , in contrast to the closely related nucleoside derived from the analogue N6-methoxyaminopurine (dZ), which was only weakly mutagenic. The 5'-triphosphate derivatives, dKTP and dZTP, were synthesized; Taq polymerase incorporated dKTP opposite both T and, less well, opposite dC in template DNA. Both analogue triphosphates produced transition mutations when added to PCR reactions. In each case, there was a large excess of AT-->GC compared to GC-->AT mutations (ratios were 15:1 for dKTP and 10:1 for dZTP). Polymerase extension times in each cycle had to be extended, consistent with a decreased rate of DNA synthesis in the presence of the analogues. This and the mutagenic ratios are discussed in terms of syn-anti inversion of the methoxyl group.
Topics: Aminoimidazole Carboxamide; Animals; Base Sequence; Cattle; DNA; DNA Primers; DNA, Bacterial; Deoxyribonucleosides; Deoxyribonucleotides; Escherichia coli; In Vitro Techniques; Molecular Sequence Data; Mutagenicity Tests; Mutagens; Polymerase Chain Reaction
PubMed: 9469819
DOI: 10.1093/nar/26.5.1144 -
Current Protocols in Nucleic Acid... Oct 2004DNA synthesis can be achieved by using O-selective methods for internucleotide bond formation. This greatly simplifies the synthesis of oligodeoxyribonucleotides by... (Review)
Review
DNA synthesis can be achieved by using O-selective methods for internucleotide bond formation. This greatly simplifies the synthesis of oligodeoxyribonucleotides by eliminating the need for nucleobase protection and deprotection steps. This unit describes strategies that can be used for DNA synthesis without base protection. The discussion includes synthesis of phosphoramidite and H-phosphonate monomers, solid-phase assembly by the phosphoramidite and H-phosphonate methods, and future prospects for DNA synthesis using N-unprotected approaches.
Topics: Base Pairing; DNA; DNA Repair; Deoxyribonucleosides; Models, Biological; Organophosphonates; Organophosphorus Compounds; Templates, Genetic
PubMed: 18428925
DOI: 10.1002/0471142700.nc0310s18 -
Chemical Research in Toxicology May 2002Estrogen 2,3- and 3,4-quinones are reactive species toward nucleophiles and Michael acceptors. As such, they can bind to DNA and induce cellular damages. As an...
Estrogen 2,3- and 3,4-quinones are reactive species toward nucleophiles and Michael acceptors. As such, they can bind to DNA and induce cellular damages. As an alkylation model, reactions of estradiol-2,3-quinone with deoxyribonucleosides were previously studied by mass spectrometry. In this work, estrogen-deoxyribonucleoside adducts were synthesized by reaction of 17beta-estradiol-2,3-quinone with deoxyguanosine or deoxyadenosine and analyzed by NMR and LC-MS(n)() in order to determine the structure and the stereochemistry of the resulting covalent adducts. Although estradiol- and estrone-2,3-quinones were previously thought to give mainly stable adducts, identification of depurinating adducts with both nucleosides, i.e., 2-OHE(2)-6(alpha,beta)-N7Gua and 2-OHE(2)-6(alpha,beta)-N7Ade, was unambiguously obtained. This is of particular interest since depurinating adducts are generated from DNA, and therefore, their amount should be correlated to the parallel formation of apurinic sites, which might play an important role in the cancer initiation process. Besides, a byproduct, i.e., 2-hydroxy-11-oxo-estradiol, corresponding to an unstable alkylation product of 2-hydroxyestradiol has been unambiguously identified and is indicative of a plausible addition process at the C9 position of catechol estrogens. The synthetic adducts will be useful as reference compounds to further elucidate the structure of adducts formed by reaction of estrogen metabolites with DNA or oligonucleotides.
Topics: Chromatography, High Pressure Liquid; Deoxyribonucleosides; Estradiol; Spectrometry, Mass, Electrospray Ionization; Static Electricity; Structure-Activity Relationship
PubMed: 12018999
DOI: 10.1021/tx015561y -
The Journal of Organic Chemistry Jul 2002The present efficient synthesis of [5'-13C]ribonucleosides and 2'-deoxy[5'-13C]ribonucleosides is characterized by the synthesis of the D-[5-13C]ribose derivative as an...
The present efficient synthesis of [5'-13C]ribonucleosides and 2'-deoxy[5'-13C]ribonucleosides is characterized by the synthesis of the D-[5-13C]ribose derivative as an intermediate via the Wittig reaction of 4-aldehydo-D-erythrose dialkyl acetals with Ph3P13CH3I-BuLi to introduce the 13C label at the 5-position of a pentose. This was followed by the highly diastereoselective osmium dihydroxylation for the preparation of 2,3-di-O-benzyl-D-[5-13C]ribose dialkyl acetal and the cyclization from D-[5-13C]ribose dialkyl acetal derivatives to the alkyl D-[5-13C]ribofuranoside derivative by the use of LiBF(4). The obtained D-[5-13C]ribose derivative was converted into [5'-13C]ribonucleosides and subsequently into the corresponding 2'-deoxynucleosides.
Topics: Carbon Isotopes; Deoxyribonucleosides; Magnetic Resonance Spectroscopy; Molecular Structure; Ribonucleosides; Stereoisomerism
PubMed: 12126398
DOI: 10.1021/jo016281q -
Brain Research Nov 1996Substances can enter the brain either directly across the blood-brain barrier or indirectly across the choroid plexuses and arachnoid membrane (blood-CSF barrier) into...
Substances can enter the brain either directly across the blood-brain barrier or indirectly across the choroid plexuses and arachnoid membrane (blood-CSF barrier) into the CSF and then by diffusion into the brain. Earlier studies have demonstrated a saturable thymidine uptake across the blood-CSF barrier, but not across the blood-brain barrier. In this study transport of [3H]thymidine across both barriers was measured in vivo by means of a bilateral vascular brain perfusion technique in the anaesthetised guinea-pig. This method allows simultaneous and quantitative measurement of slowly penetrating solutes into both brain and CSF, under controlled conditions of arterial inflow. The results of the present study carried out over perfusion periods of up to 30 min indicated a progressive uptake of [3H]thymidine into brain and CSF, which was found to be significantly greater than the transport of D-[14C]mannitol (a plasma space marker). Furthermore, the addition of 1 mM unlabelled thymidine in the perfusate caused saturation of [3H]thymidine uptake into both brain and CSF. In conclusion, these findings suggest that thymidine can cross both the blood-brain and blood-CSF barriers in the guinea-pig by carrier-mediated transport systems.
Topics: Animals; Blood-Brain Barrier; Body Water; Capillary Permeability; Cerebrovascular Circulation; Deoxyribonucleosides; Guinea Pigs; Kinetics; Mannitol; Perfusion; Solubility; Thymidine
PubMed: 9001727
DOI: 10.1016/s0006-8993(96)00930-4 -
Nucleic Acids Symposium Series 1995From readily available starting materials, the preparation and characterization of a variety of pyrimidine 2', 3'-dideoxyribo-, 2'-deoxyribo-, 3'-deoxyribo- and ribo-...
From readily available starting materials, the preparation and characterization of a variety of pyrimidine 2', 3'-dideoxyribo-, 2'-deoxyribo-, 3'-deoxyribo- and ribo- N-protected 4'-aza nucleosides is reported. None was found to possess any significant antiviral activity.
Topics: Aza Compounds; Deoxyribonucleosides; Molecular Structure; Pyrrolidonecarboxylic Acid; Ribonucleosides
PubMed: 8841526
DOI: No ID Found -
Journal of the American Chemical Society Oct 2022A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C-H functionalization of...
A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C-H functionalization of diverse (hetero)aromatics with dibenzothiophene--oxide followed by the Negishi cross-cooupling with bis(4,6-dichloropyrimidin-5-yl)zinc. This cross-coupling afforded a series of (het)aryl-pyrimidines that were converted to fused deazapurine heterocycles through azidation and thermal cyclization. The fused heterocycles were glycosylated to the corresponding 2'-deoxy- and ribonucleosides, and a series of derivatives were prepared by nucleophilic substitutions at position 4. Four series of new polycyclic thieno-fused 7-deazapurine nucleosides were synthesized using this strategy. Most of the deoxyribonucleosides showed good cytotoxic activity, especially for the CCRF-CEM cell line. Phenyl- and thienyl-substituted thieno-fused 7-deazapurine nucleosides were fluorescent, and the former one was converted to 2'-deoxyribonucleoside triphosphate for enzymatic synthesis of labeled oligonucleotides.
Topics: Nucleosides; Cell Line, Tumor; Ribonucleosides; Pyrimidines; Oxides; Zinc; Oligonucleotides; Deoxyribonucleosides; Purine Nucleosides
PubMed: 36245092
DOI: 10.1021/jacs.2c07517