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Nucleosides, Nucleotides & Nucleic Acids Mar 2017Reported is an efficient synthesis of adenyl and uridyl 5'-tetrachlorophthalimido-5'-deoxyribonucleosides, and guanylyl 5'-azido-5'-deoxyribonucleosides, which are...
Reported is an efficient synthesis of adenyl and uridyl 5'-tetrachlorophthalimido-5'-deoxyribonucleosides, and guanylyl 5'-azido-5'-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5'-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5'-hydroxyl with an azido group. The resulting compounds were converted to 5'-amino-5'-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2',3'-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5'-tetrachlorophthalimido and 5'-azido demonstrated increased antibacterial effect.
Topics: Adenosine; Anti-Bacterial Agents; Azides; Chemistry Techniques, Synthetic; Deoxyribonucleosides; Drug Evaluation, Preclinical; Microbial Sensitivity Tests; Neisseria meningitidis; Phthalimides; Uridine
PubMed: 28045593
DOI: 10.1080/15257770.2016.1250906 -
Pharmacology & Therapeutics 1987
Review
Topics: Alkylation; Animals; Chemical Phenomena; Chemistry; Deoxyribonucleosides; Humans; Pyrimidines
PubMed: 3317451
DOI: 10.1016/0163-7258(87)90011-8 -
Journal of Hazardous Materials Feb 2017Bisphenol A is a monomer used in the manufacture of polycarbonate plastic products, epoxy resin-based food can liners and flame retardants. To determine the genotoxic...
Bisphenol A is a monomer used in the manufacture of polycarbonate plastic products, epoxy resin-based food can liners and flame retardants. To determine the genotoxic potential of bisphenol A, the mechanism of the reactions between the reactive electophilic bisphenol A 3,4-quinone (BPAQ) with glutathione and ribonucleosides/deoxyribonucleosides were studied. The obtained results demonstrated that BPAQ reacted with 2'-deoxyguanosine (dG)/guanosine (G), 2'-deoxyadenosine (dA)/adenosine (A), but not with 2'-deoxycytidine (dC)/cytidine (C) and thymidine (T)/uridine (U) in aqueous acetic acid. The reactions were accompanied by loss of deoxyribose, and the rate of depurination by deoxyribonucleoside adducts were faster than that of ribonucleoside adducts. In mixtures of ribonucleosides and deoxyribonucleosides treated with BPAQ, reactions occurred more readily with dG/G than dA/A. The structures of the modified bases were confirmed by electrospray ionization tandem mass spectrometry (ESI-MS/MS). We also found that BPAQ reacted readily with glutathione (GSH) in aqueous acetic acid, and characterized the BPAQ-GSH conjugate by ESI-MS/MS. The in vitro data of depurinating DNA/RNA adducts and BPAQ-GSH adducts may provide appropriate reference for the identification of BPAQ adducts in environmental and biological systems.
Topics: Benzhydryl Compounds; Benzoquinones; Binding Sites; DNA Adducts; Deoxyribonucleosides; Environmental Pollutants; Glutathione; Phenols; Ribonucleosides; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 26971050
DOI: 10.1016/j.jhazmat.2016.03.015 -
Archives of Surgery (Chicago, Ill. :... May 1999We hypothesized that a topical mixture of purified deoxyribonucleosides would accelerate wound healing in an open wound model.
HYPOTHESIS
We hypothesized that a topical mixture of purified deoxyribonucleosides would accelerate wound healing in an open wound model.
DESIGN
Full-thickness 6-mm wounds were made on the ears of young adult rabbits. In some experiments, 2 of the 3 arteries in each ear were divided to induce wound ischemia.
INTERVENTIONS
An equiweight mixture containing all 4 of the major deoxyribonucleosides (deoxyadenosine, deoxycytidine, deoxyguanosine, and thymidine), designated PN105, or other subgroups of deoxyribonucleosides, or vehicle (saline) was applied to wounds on 1 ear every 2 days, with the other ear serving as a control.
MAIN OUTCOME MEASURES
Wound tissue was processed for histological examination 7 days after the initial wounding. Granulation tissue formation and epithelialization were measured in histological cross sections of wounds.
RESULTS
Treatment of wounds with PN105 resulted in a 191% increase in total new granulation tissue (P<.05) and a higher incidence of complete wound reepithelialization (67% vs 37%; P<.05) when compared with controls, and a similar increase under ischemic conditions on day 7. Wound ischemia markedly impairs healing; PN 105 treatment resulted in a 242% increase in the amount of new granulation tissue formed by day 7 in ischemic wounds, relative to the appropriate controls (P<.05). All 4 of the major deoxyribonucleosides were required for optimum activity; mixtures with 3 or 2 were less active or inactive.
CONCLUSIONS
Topically applied deoxyribonucleosides reproducibly accelerate wound healing in normal and ischemic wounds, and to a magnitude equivalent to that of recombinant growth factors such as platelet-derived growth factor, previously studied in this model. In view of their safety, availability, and efficacy, deoxyribonucleosides hold considerable promise for improving healing of chronic wounds.
Topics: Acrylic Resins; Administration, Topical; Animals; Deoxyribonucleosides; Female; Rabbits; Time Factors; Wound Healing
PubMed: 10323424
DOI: 10.1001/archsurg.134.5.520 -
PLoS Pathogens Dec 2023Staphylococcus aureus is a dangerous pathogen that evolved refined immuno-evasive strategies to antagonize host immune responses. This involves the biogenesis of...
Staphylococcus aureus is a dangerous pathogen that evolved refined immuno-evasive strategies to antagonize host immune responses. This involves the biogenesis of death-effector deoxyribonucleosides, which kill infectious foci-penetrating macrophages. However, the exact mechanisms whereby staphylococcal death-effector deoxyribonucleosides and coupled imbalances of intracellular deoxyribonucleotide species provoke immune cell death remain elusive. Here, we report that S. aureus systematically promotes an overload of deoxyribonucleotides to trigger mitochondrial rupture in macrophages, a fatal event that induces assembly of the caspase-9-processing apoptosome and subsequent activation of the intrinsic pathway of apoptosis. Remarkably, genetic disruption of this cascade not only helps macrophages coping with death-effector deoxyribonucleoside-mediated cytotoxicity but also enhances their infiltration into abscesses thereby ameliorating pathogen control and infectious disease outcomes in laboratory animals. Combined with the discovery of protective alleles in human CASP9, these data highlight the role of mitochondria-centered apoptosis during S. aureus infection and suggest that gene polymorphisms may shape human susceptibility toward a predominant pathogen.
Topics: Animals; Humans; Staphylococcus aureus; Nucleotides; Phagocytes; Cell Death; Apoptosis; Mitochondria; Deoxyribonucleosides
PubMed: 38157331
DOI: 10.1371/journal.ppat.1011892 -
Applied Microbiology and Biotechnology Aug 20062'-Deoxyribonucleosides are important as building blocks for the synthesis of antisense drugs, antiviral nucleosides, and 2'-deoxyribonucleotides for polymerase chain...
2'-Deoxyribonucleosides are important as building blocks for the synthesis of antisense drugs, antiviral nucleosides, and 2'-deoxyribonucleotides for polymerase chain reaction. The microbial production of 2'-deoxyribonucleosides from simple materials, glucose, acetaldehyde, and a nucleobase, through the reverse reactions of 2'-deoxyribonucleoside degradation and the glycolytic pathway, was investigated. The glycolytic pathway of baker's yeast yielded fructose 1,6-diphosphate from glucose using the energy of adenosine 5'-triphosphate generated from adenosine 5'-monophosphate through alcoholic fermentation with the yeast. Fructose 1,6-diphosphate was further transformed to 2-deoxyribose 5-phosphate in the presence of acetaldehyde by deoxyriboaldolase-expressing Escherichia coli cells via D-glyceraldehyde 3-phosphate. E. coli transformants expressing phosphopentomutase and nucleoside phosphorylase produced 2'-deoxyribonucleosides from 2-deoxyribose 5-phosphate and a nucleobase via 2-deoxyribose 1-phosphate through the reverse reactions of 2'-deoxyribonucleoside degradation. Coupling of the glycolytic pathway and deoxyriboaldolase-catalyzing reaction efficiently supplied 2-deoxyribose 5-phosphate, which is a key intermediate for 2'-deoxyribonucleoside synthesis. 2'-Deoxyinosine (9.9 mM) was produced from glucose, acetaldehyde, and adenine through three-step reactions via fructose 1,6-diphosphate and then 2-deoxyribose 5-phosphate, the molar yield as to glucose being 17.8%.
Topics: Acetaldehyde; Adenine; Biotechnology; Deoxyribonucleosides; Escherichia coli; Glucose; Glycolysis; Inosine; Ribosemonophosphates; Saccharomyces cerevisiae
PubMed: 16283293
DOI: 10.1007/s00253-005-0205-5 -
Current Protocols in Nucleic Acid... Oct 2006The phosphorylating reagent bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite is prepared in three steps from commercial methyl thioglycolate...
The phosphorylating reagent bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite is prepared in three steps from commercial methyl thioglycolate and diisopropylphosphoramidous dichloride. The phosphorylating reagent has been used successfully in the solid-phase synthesis of deoxyribonucleoside 5'-/3'-phosphate or -thiophosphate monoesters and oligonucleotide 5'-phosphate/-thiophosphate monoesters. Bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite has also been employed in the construction of a thermolytic dinucleotide prodrug model to evaluate the ability of the reagent to produce thermosentive oligonucleotide prodrugs under mild temperature conditions ( approximately 25 degrees C) for potential therapeutic applications.
Topics: Chromatography, High Pressure Liquid; DNA; Deoxyribonucleosides; Phosphorylation
PubMed: 18428949
DOI: 10.1002/0471142700.nc1306s26 -
Current Protocols in Nucleic Acid... Jul 2005Ribonucleosides are converted into 2'-deoxyribonucleosides in good yields by a four-step procedure. Selective protection of the 3'- and 5'-hydroxyl groups with...
Ribonucleosides are converted into 2'-deoxyribonucleosides in good yields by a four-step procedure. Selective protection of the 3'- and 5'-hydroxyl groups with 1,3-dichloro-1,1,3,3-tetraisopropyl-1,3-disiloxane is followed by functionalization of the 2'-hydroxyl group with phenoxythiocarbonyl chloride. Free radical-mediated reductive C2'-O2' bond cleavage of these 3',5'-O-TPDS-2'-O-PTC-nucleoside derivatives with tributyltin hydride, followed by removal of the silyl protecting group with tetrabutylammonium fluoride, provides the 2'-deoxyribonucleosides. Adenosine, cytidine, guanosine, and uridine are converted into dA, dC, dG, and dU in overall yields of 60% to 80%. Use of tributyltin deuteride in the reductive cleavage step gives 2'-deuterio-2'-deoxyadenosine in 81% yield from adenosine with >85% retention of configuration at C2'. Application of this four-step protocol with nucleoside analogs is straightforward.
Topics: Deoxyribonucleosides; Free Radicals; Molecular Structure; Oxidation-Reduction; Ribonucleosides
PubMed: 18428933
DOI: 10.1002/0471142700.nc0111s21 -
Molecules (Basel, Switzerland) Jan 2013The advantages and disadvantages of existing approaches to the synthesis of oligodeoxyribonucleotides (ODN) are discussed focusing on large-scale methods. The liquid... (Review)
Review
The advantages and disadvantages of existing approaches to the synthesis of oligodeoxyribonucleotides (ODN) are discussed focusing on large-scale methods. The liquid phase and solid supported synthesis and the synthesis on soluble polymers are discussed. Different problems concerning the methods and implementation of the ODN synthesis are outlined depending on goals of using target oligomers.
Topics: Click Chemistry; Deoxyribonucleosides; Oligodeoxyribonucleotides; Solid-Phase Synthesis Techniques
PubMed: 23322070
DOI: 10.3390/molecules18011063 -
NatureThe retrovirus that causes AIDS has revealed enough of its life history for a variety of therapeutic strategies to be apparent. Some of these are suitable for immediate... (Review)
Review
The retrovirus that causes AIDS has revealed enough of its life history for a variety of therapeutic strategies to be apparent. Some of these are suitable for immediate application in clinical trials or have already yielded positive results in some patients.
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; DNA, Viral; Deoxycytidine; Deoxyribonucleosides; HIV; Humans; RNA, Viral; Reverse Transcriptase Inhibitors; T-Lymphocytes; Thymidine; Viral Proteins; Virus Replication; Zalcitabine; Zidovudine
PubMed: 2434858
DOI: 10.1038/325773a0