5-Hydroxy-2'-deoxyuridine
(Synonyms: 5-OHdU) 目录号 : GC60529
5-Hydroxy-2'-deoxyuridine(5-OHdU)是一种2'-Deoxycytidine的主要稳定氧化产物。5-Hydroxy-2'-deoxyuridine可以通过DNA聚合酶在体外掺入DNA。
Cas No.:5168-36-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
5-Hydroxy-2'-deoxyuridine (5-OHdU) is a major stable oxidation product of 2'-Deoxycytidine. 5-Hydroxy-2'-deoxyuridine can be incorporated into DNA in vitro by DNA polymerase[1].
To study the specificity of nucleotide incorporation opposite 5-hydroxypyrimidines in template DNA, 18- and 45-member oligodeoxyribonucleotides, containing an internal 2'-deoxy-5-hydroxyuridine (5-OHdU) in two different sequence contexts, were used. Translesion synthesis past 2'-deoxy-5-hydroxyuridine (5-OHdU) in both oligonucleotides occurred, but pauses both opposite, and one nucleotide prior to, the modified base in the template is observed. The specificity of nucleotide incorporation opposite 2'-deoxy-5-hydroxyuridine (5-OHdU) in the template is sequence context dependent. In one sequence context, dA is the principal nucleotide incorporated opposite 2'-deoxy-5-hydroxyuridine (5-OHdU). However in a second sequence context, dC is the predominant base incorporated opposite 2'-deoxy-5-hydroxyuridine (5-OHdU). In that same sequence context, dC is also the predominant nucleotide incorporated opposite 2'-deoxy-5-hydroxyuridine (5-OHdU)[1].
[1]. Purmal AA, et al. Major oxidative products of cytosine, 5-hydroxycytosine and 5-hydroxyuracil, exhibit sequence context-dependent mispairing in vitro. Nucleic Acids Res. 1994 Jan 11;22(1):72-8.
| Cas No. | 5168-36-5 | SDF | |
| 别名 | 5-OHdU | ||
| Canonical SMILES | OC[C@@H]1[C@H](C[C@H](N2C(NC(C(O)=C2)=O)=O)O1)O | ||
| 分子式 | C9H12N2O6 | 分子量 | 244.2 |
| 溶解度 | Water: 10 mg/mL (40.95 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.095 mL | 20.475 mL | 40.95 mL |
| 5 mM | 0.819 mL | 4.095 mL | 8.19 mL |
| 10 mM | 0.4095 mL | 2.0475 mL | 4.095 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
New substrates for old enzymes. 5-Hydroxy-2'-deoxycytidine and 5-Hydroxy-2'-deoxyuridine are substrates for Escherichia coli endonuclease III and formamidopyrimidine DNA N-glycosylase, while 5-Hydroxy-2'-deoxyuridine is a substrate for uracil DNA N-glycosylase
J Biol Chem 1994 Jul 22;269(29):18814-20.PMID:8034633doi
5-Hydroxy-2'-deoxycytidine (5-OHdC) and 5-Hydroxy-2'-deoxyuridine (5-OHdU) are major products of oxidative DNA damage with mutagenic potential. Until now, no enzymatic activity responsible for their removal has been identified. We report here that both 5-OHdC and 5-OHdU are substrates for Escherichia coli endonuclease III and formamidopyrimidine DNA N-glycosylase (FPG). 5-OHdU is also a substrate for uracil DNA N-glycosylase. Consistent with their mechanisms of action on previously described substrates, endonuclease III removes 5-OHdC and 5-OHdU via a N-glycosylase/beta-elimination reaction, FPG follows a N-glycosylase/beta,delta-elimination reaction, and uracil N-glycosylase removes 5-OHdU by N-glycosylase action leaving behind an abasic site. Endonuclease III removes both lesions more efficiently than FPG, and both endonuclease III and FPG remove 5-OHdC slightly more efficiently than 5-OHdU. Uracil DNA N-glycosylase removes 5-OHdU more efficiently than the other two enzymes and has no activity on 5-OHdC even when present in great excess. Analysis of crude extracts obtained from wild type and endonuclease III deletion mutants of E. coli correlated well with data obtained with the purified enzymes.
5-Selenocyanato and 5-trifluoromethanesulfonyl derivatives of 2'-deoxyuridine: synthesis, radiation and computational chemistry as well as cytotoxicity
RSC Adv 2018 Jun 12;8(38):21378-21388.PMID:35539961DOI:10.1039/c8ra03172j.
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.
Oxidation of 5-hydroxypyrimidine nucleosides to 5-hydroxyhydantoin and its alpha-hydroxy-ketone isomer
Chem Res Toxicol 2005 Aug;18(8):1332-8.PMID:16097807DOI:10.1021/tx050121i.
The reaction of hydroxyl radicals with 2'-deoxycytidine (dCyd), as well as the decomposition of dCyd radical cations, leads to a complex mixture of oxidation products in aqueous aerated solutions. The oxidation of dCyd gives products with a relatively low oxidation potential that are highly susceptible to further oxidation, including 5-hydroxy-2'-deoxycytidine (5-oh-dCyd) and 5-Hydroxy-2'-deoxyuridine (5-oh-dUrd). Previously, we showed that the oxidation of 2'-deoxyuridine (dUrd) involves the formation of dialuric acid and isodialuric acid intermediates, followed by ring contraction to N1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxyhydantoin (5-oh-dHyd). In this work, we have examined the oxidation of 5-oh-dCyd and 5-oh-dUrd in greater detail. The oxidation of these substrates by Br2 led to a similar profile of intermediate and stable products indicating that the dialuric and isodialuric acid derivatives of dCyd largely undergo deamination before they transform into 5-oh-dHyd. Analysis of the final mixture of oxidation products by HPLC revealed the formation of two novel products. On the basis of NMR and MS, these products were identified as the diastereomers of N1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxyimidazolidine-2,5-dione (iso-4-oh-dHyd). These products arise from alpha-hydroxy-ketone isomerization of 5-oh-dHyd. The isomerization of 5-oh-dHyd to iso-4-oh-dHyd was reversible, and each diastereomer produced a specific diastereomer of the other structural isomer. The rate of isomerization was accelerated in going from pH 5 to pH 9, whereas all isomers decomposed at higher pH. In contrast, interconversion between each pair of diastereomers was minor. Thus, we conclude that the oxidation of 5-oh-dCyd or 5-oh-dUrd gives a mixture of four isomers of 5-oh-dHyd and iso-4-oh-dHyd as final products. The biological consequences of dCyd oxidation may ultimately depend on the effects of these products.
Synergistic enhancement of 5-fluorouracil cytotoxicity by deoxyuridine analogs in cancer cells
Oncoscience 2015 Feb 9;2(3):272-84.PMID:25897430DOI:10.18632/oncoscience.125.
5-Fluorouracil (FU) is a halogenated nucleobase analog that is widely used in chemotherapy. Here we show that 5-hydroxymethyl-2'-deoxyuridine (hmUdR) synergistically enhances the activity of FU in cell lines derived from solid tumors but not normal tissues. While the cytotoxicity of FU and hmUdR was not directly related to the amount of the modified bases incorporated into cellular DNA, incubation with this combination resulted in dramatic increase in the number of single strand breaks in replicating cancer cells, leading to NAD-depletion as consequence of poly(ADP-ribose) synthesis and S phase arrest. Cell death resulting from the base/nucleoside combination did not occur by apoptosis, autophagy or necroptosis. Instead, the cells die via necrosis as a result of NAD depletion. The FU-related nucleoside analog, 5-fluoro-2'-deoxyuridine, also displayed synergy with hmUdR, whereas hmUdR could not be replaced by 5-hydroxymethyluracil. Among other 5-modified deoxyuridine analogs tested, 5-formyl-2'-deoxyuridine and, to a lesser extent, 5-Hydroxy-2'-deoxyuridine, also acted synergistically with FU, whereas 5-hydroxyethyl-2'-deoxyuridine did not. Together, our results have revealed an unexpected synergistic interaction between deoxyuridine analogs and FU in a cancer cell-specific manner, and suggest that these novel base/nucleoside combinations could be developed into improved FU-based chemotherapies.
Oxidation of 5-Hydroxy-2'-deoxyuridine into isodialuric acid, dialuric acid, and hydantoin products
J Am Chem Soc 2004 Jun 2;126(21):6548-9.PMID:15161271DOI:10.1021/ja049438f.
Oxidation products of cytosine, including 5-hydroxycytosine and 5-hydroxyuracil, are highly susceptible to subsequent oxidation. Here, the oxidation products of 5-Hydroxy-2'-deoxyuridine have been studied by NMR and MS analyses. The initial products were diastereomers of isodialuric acid nucleoside. These products subsequently decomposed into corresponding dialuric acid derivatives at neutral pH. The position of the carbonyl and hydroxyl groups, at C5 and C6 for isodialuric acid and at C6 and C5 for dialuric acid derivatives, respectively, was determined by 1H- and 13C NMR analyses. In addition, these analyses revealed that the carbonyl groups of both isodaluric and dialuric acid derivatives exist in their fully hydrated form in aqueous solution. Finally, the dialuric acid derivatives were observed to undergo subsequent decomposition into the corresponding 5-hydroxyhydantoin derivatives. Studies of a trinucleotide containing 5-hydroxyuracil suggest that the reactions described herein for the monomer can be extrapolated to DNA.