5168-36-5

Usage

Uses

Used in Mitochondrial DNA Repair:
5-HYDROXY-2'-DEOXYURIDINE is used as a key component in the base excision repair (BER) mechanism for maintaining the integrity of mitochondrial DNA. Its involvement in the BER process helps to correct DNA damage, preventing the accumulation of mutations and preserving the proper functioning of mitochondria.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 5-HYDROXY-2'-DEOXYURIDINE is used as a research tool for studying the mechanisms of DNA repair and the development of potential therapeutic agents targeting mitochondrial dysfunction. Understanding its role in the BER process can lead to the discovery of new drugs that enhance DNA repair or protect against DNA damage, which could have applications in treating various diseases associated with mitochondrial dysfunction.
Used in Diagnostic Applications:
5-HYDROXY-2'-DEOXYURIDINE can also be used in diagnostic applications to detect and monitor mitochondrial DNA damage in various diseases. By measuring the levels of this modified nucleoside in biological samples, researchers and clinicians can gain insights into the extent of DNA damage and the effectiveness of potential treatments targeting mitochondrial repair mechanisms.

InChI:InChI=1/C9H12N2O6/c12-3-6-4(13)1-7(17-6)11-2-5(14)8(15)10-9(11)16/h2,4,6-7,12-14H,1,3H2,(H,10,15,16)

Upstream product

• 59-14-3 5-bromo-2'-deoxyuridine 
• 951-77-9 2'-Deoxycytidine 
• 58-96-8 uridine 
• 951-78-0 2'-deoxyuridine 
• 6974-32-9 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 

Downstream Products

• 151361-85-2 5-(Trifluoromethanesulfonyloxy)-2'-deoxyuridine 
• 77355-97-6 5-<(cyanomethylene)oxy>-2'-deoxyuridine 
• 77355-98-7 3-(cyanomethyl)-5-hydroxy-2'-deoxyuridine 
• 77355-99-8 3-(cyanomethyl)-5-<(cyanomethylene)oxy>-2'-deoxyuridine 
• 76462-96-9 1-(2'-deoxy-β-D-ribofuranosyl)-5-<<2,2,6,6-tetramethyl-1-(oxyl)piperidin-4-yl>amino>pyrimidine-2,4(1H,3H)-dione 
• 20636-41-3 5-hydroxyuracil 
• 77181-58-9 5-carbamoylmethyl-2'-deoxyuridine 
• 61135-33-9 2'-deoxy-5-ethynyluridine 
• 151361-96-5 Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-[2,4-dioxo-5-(4-trifluoromethyl-phenylethynyl)-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-3-yl ester 
• 151361-86-3 3',5'-Di-O-acetyl-5-(trifluoromethanesulfonyloxy)-2'-deoxyuridine 
• 151361-94-3 Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-[5-(3,5-difluoro-phenylethynyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-tetrahydro-furan-3-yl ester 

Relevant academic research and scientific papers

5-Selenocyanato and 5-trifluoromethanesulfonyl derivatives of 2′-deoxyuridine: Synthesis, radiation and computational chemistry as well as cytotoxicity

5-Selenocyanato-2′-deoxyuridine (SeCNdU) and 5-trifluoromethanesulfonyl-2′-deoxyuridine (OTfdU) have been synthesized and their structures have been confirmed with NMR and MS methods. Both compounds undergo dissociative electron attachment (DEA) when irradiated with X-rays in an aqueous solution containing a hydroxyl radical scavenger. The DEA yield of SeCNdU significantly exceeds that of 5-bromo-2′-deoxyuridine (BrdU), remaining in good agreement with the computationally revealed profile of electron-induced degradation. The radiolysis products indicate, in line with theoretical predictions, Se-CN bond dissociation as the main reaction channel. On the other hand, the DEA yield for OTfdU is slightly lower than the degradation yield measured for BrdU, despite the fact that the calculated driving force for the electron-induced OTfdU dissociation substantially overpasses the thermodynamic stimulus for BrdU degradation. Moreover, the calculated DEA profile suggests that the electron attachment induced formation of 5-hydroxy-2′-deoxyuridine (OHdU) from OTfdU, while 2′-deoxyuridine (dU) is mainly observed experimentally. We explained this discrepancy in terms of the increased acidity of OTfdU resulting in efficient deprotonation of the N3 atom, which brings about the domination of the OTfdU(N3-H)- anion in the equilibrium mixture. As a consequence, electron addition chiefly leads to the radical dianion, OTfdU(N3-H)2-, which easily protonates at the C5 site. As a result, the C5-O rather than O-S bond undergoes dissociation, leading to dU, observed experimentally. A negligible cytotoxicity of the studied compounds toward the MCF-7 cell line at the concentrations used for cell labelling calls for further studies aiming at the clinical use of the proposed derivatives.

5-Modified-2'-dU and 2'-dC as mutagenic Anti HIV-1 proliferation agents: Synthesis and activity

With the goal of limiting HIV-I proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrrolidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified on the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-I. proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds plus two additional ones (5-carbamoyl-2'-dU (la) and 5-carbamoylmethyl-2'-dU (1b)) were potent, inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1. genome.

Synthesis and characterization of isotopically enriched pyrimidine deoxynucleoside oxidation damage products

Oxidative damage to DNA is an established source of genomic instability. In this paper, we describe the synthesis and characterization of several pyrimidine deoxynucleoside oxidation damage products, enriched with stable isotopes. These products include the 2'-deoxynucleoside derivatives of 5- (hydroxymethyl)uracil, 5-formyluracil, 5-hydroxyuracil, 5-(hydroxymethyl)- cytosine, 5-formylcytosine, and 5-hydroxycytosine. The common precursor is 2'-deoxy-2''-deutero[1,3-15N]uridine. Additional stable isotopes are added during functional group conversions. Characterization of these derivatives includes mass spectrometry and 1H and 15N NMR spectroscopy. Proton and nitrogen NMR studies reported here allow an examination of the influence of the modification on sugar conformation and tautomeric equilibrium, properties likely to be important in understanding the biological consequences of these DNA damage products.

Measurement of oxidative damage at pyrimidine bases in γ-irradiated DNA

Oxidized nucleobases represent one of the main classes of damage induced in DNA by ionizing radiation. Emphasis was placed in this work on the measurement of four oxidized pyrimidine bases, including 5- (hydroxymethyl)uracil (5-HMUra), 5-formyluracil (5-ForUra), 5-hydroxy- cytosine (5-OHCyt), and 5-hydroxyuracil (5-OHUra), in isolated DNA upon exposure to γ radiation in aerated aqueous solution. For this purpose, both high performance liquid chromatography associated with electrochemical detection (HPLC-EC) and gas chromatography coupled to mass spectrometry (GC- MS) were used. Conditions of hydrolysis of the N-glycosidic bond were carefully checked in order to achieve a quantitative release of the lesions. We showed that 60% formic acid treatment leads to the decomposition of the four lesions studied. On the other hand, hydrolysis based on the use of either 88% formic acid or 70% hydrogen fluoride in pyridine (HF/Pyr) allowed the quantitative release of the modified bases, with the exception of 5- HMUra when the latter reagent was utilized. A dose course study of the radiation-induced formation of 5-HMUra and 5-ForUra in DNA by using the GC- MS assay showed that the latter lesion was produced in a 2.1-fold higher yield than the former one. HF/Pyr and 88% formic acid hydrolysis provided similar results for 5-ForUra, indicating the reliability of both techniques for the measurement of this lesion. For 5-OHUra and 5-OHCyt, the level of modification determined by GC-MS analysis was higher after 88% formic acid treatment than upon HF/Pyr hydrolysis. When DNA was enzymatically digested and analyzed by HPLC-EC for 5-OHdCyd and 5-OHdUrd, the results were very close to those obtained by GC-MS following HF/Pyr treatment. It was concluded that additional amounts of both 5-OHUra and 5-OHCyt are produced during the 88% formic acid treatment from radiation-induced 5,6-saturated pyrimidine precursors. It is likely that cytosine and uracil diols are involved in this reaction. The radiochemical yields of formation (in μmol · J-1) for the products studied are in the following decreasing order: 5-ForUra (0.0083) > 5-OHCyt (0.0046) > 5-HMUra (0.0039) > 5-OHUra (0.0035).