C2'-氢原子提取后RNA链的快速断裂。
Rapid RNA strand scission following C2'-hydrogen atom abstraction.
作者信息
Paul Rakesh, Greenberg Marc M
机构信息
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
出版信息
J Am Chem Soc. 2015 Jan 21;137(2):596-9. doi: 10.1021/ja511401g. Epub 2015 Jan 12.
Abstract
C2'-Nucleotide radicals have been proposed as key intermediates in direct strand break formation in RNA exposed to ionizing radiation. Uridin-2'-yl radical (1) was independently generated in single- and double-stranded RNA via photolysis of a ketone precursor. Direct stand breaks result from heterolytic cleavage of the adjacent C3'-carbon-oxygen bond. Trapping of 1 by O2 or β-mercaptoethanol (1 M) does not compete with strand scission, indicating that phosphate elimination is >10(6) s(-1). Uracil loss also does not compete with strand scission. When considered in conjunction with reports that nucleobase radicals produce 1, this chemistry explains why RNA is significantly more susceptible to strand scission by ionizing radiation (hydroxyl radical) than is DNA.
摘要
C2'-核苷酸自由基被认为是暴露于电离辐射的RNA中直接形成链断裂的关键中间体。通过酮前体的光解在单链和双链RNA中独立产生尿苷-2'-基自由基（1）。直接链断裂是由相邻C3'-碳-氧键的异裂裂解引起的。O2或β-巯基乙醇（1 M）对1的捕获不与链断裂竞争，表明磷酸消除速率>10(6) s(-1)。尿嘧啶的损失也不与链断裂竞争。结合核碱基自由基产生1的报道来看，这种化学过程解释了为什么RNA比DNA更容易受到电离辐射（羟基自由基）导致的链断裂。
相似文献
1
Rapid RNA strand scission following C2'-hydrogen atom abstraction.C2'-氢原子提取后RNA链的快速断裂。
J Am Chem Soc. 2015 Jan 21;137(2):596-9. doi: 10.1021/ja511401g. Epub 2015 Jan 12.
2
Mechanistic Studies on RNA Strand Scission from a C2'-Radical.C2'-自由基引发的 RNA 链断裂的机制研究
J Org Chem. 2016 Oct 7;81(19):9199-9205. doi: 10.1021/acs.joc.6b01760. Epub 2016 Sep 26.
3
Direct strand scission in double stranded RNA via a C5-pyrimidine radical.通过 C5-嘧啶自由基对双链 RNA 进行直接链断裂。
J Am Chem Soc. 2012 Feb 29;134(8):3917-24. doi: 10.1021/ja300044e. Epub 2012 Feb 15.
4
Product and mechanistic analysis of the reactivity of a C6-pyrimidine radical in RNA.C6-嘧啶碱基在 RNA 中反应活性的产物和机理分析。
J Am Chem Soc. 2011 Apr 6;133(13):5152-9. doi: 10.1021/ja200317w. Epub 2011 Mar 10.
5
Direct strand scission from a nucleobase radical in RNA.RNA 中碱基自由基的直接链断裂。
J Am Chem Soc. 2010 Mar 24;132(11):3668-9. doi: 10.1021/ja100281x.
6
Hydrogen abstraction from deoxyribose by a neighbouring uracil-5-yl radical.相邻的尿嘧啶-5-基自由基从脱氧核糖中夺取氢。
Phys Chem Chem Phys. 2007 Dec 7;9(45):5975-9. doi: 10.1039/b711083a. Epub 2007 Sep 27.
7
Mechanisms Responsible for High Energy Radiation Induced Damage to Single-Stranded DNA Modified by Radiosensitizing 5-Halogenated Deoxyuridines.放射增敏性5-卤代脱氧尿苷修饰的单链DNA受高能辐射损伤的相关机制
J Phys Chem B. 2016 Mar 17;120(10):2649-57. doi: 10.1021/acs.jpcb.5b11432. Epub 2016 Mar 3.
8
Independent generation and reactivity of uridin-2'-yl radical.尿苷-2'-基自由基的独立生成与反应活性。
J Org Chem. 2014 Nov 7;79(21):10303-10. doi: 10.1021/jo501916r. Epub 2014 Oct 17.
9
Distinct hydroxy-radical-induced damage of 3'-uridine monophosphate in RNA: a theoretical study.RNA中3'-尿苷单磷酸的独特羟基自由基诱导损伤：一项理论研究。
Chemistry. 2009;15(10):2394-402. doi: 10.1002/chem.200801654.
10
Benzoyl peroxide-induced damage to DNA and its components: direct evidence for the generation of base adducts, sugar radicals, and strand breaks.过氧化苯甲酰对DNA及其组分的损伤：碱基加合物、糖自由基和链断裂生成的直接证据。
Arch Biochem Biophys. 1996 Aug 1;332(1):79-91. doi: 10.1006/abbi.1996.0319.
引用本文的文献
1
Photochemical and Single Electron Transfer Generation of 2'-Deoxycytidin-4-yl Radical from Oxime Esters.肟酯的光化学和单电子转移生成 2'-脱氧胞苷-4-基自由基。
J Org Chem. 2023 Jun 2;88(11):7381-7390. doi: 10.1021/acs.joc.3c00646. Epub 2023 May 23.
2
Site-selective redox isomerizations of furanosides using a combined arylboronic acid/photoredox catalyst system.使用芳基硼酸/光氧化还原催化剂组合体系对呋喃糖苷进行位点选择性氧化还原异构化反应。
Chem Sci. 2020 Jan 3;11(6):1531-1537. doi: 10.1039/c9sc05173b.
3
Independent Photochemical Generation and Reactivity of Nitrogen-Centered Purine Nucleoside Radicals from Hydrazines.独立光化学生成和含氮嘌呤核苷自由基的肼反应活性。
Org Lett. 2017 Dec 1;19(23):6444-6447. doi: 10.1021/acs.orglett.7b03368. Epub 2017 Nov 10.
4
Reactivity of Nucleic Acid Radicals.核酸自由基的反应活性。
Adv Phys Org Chem. 2016;50:119-202. doi: 10.1016/bs.apoc.2016.02.001.
5
Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, β-Fragmentation: Independent Generation and Reactivity of the 2'-Deoxyadenosin- N6-yl Radical.通过串联 Norrish 型 I 光解、β-断裂生成氨基自由基：2'-脱氧腺苷-N6-基自由基的独立生成和反应性。
J Org Chem. 2017 Apr 7;82(7):3571-3580. doi: 10.1021/acs.joc.7b00093. Epub 2017 Mar 20.
6
Pyrimidine Nucleobase Radical Reactivity in DNA and RNA.DNA和RNA中嘧啶核苷酸碱基的自由基反应活性
Radiat Phys Chem Oxf Engl 1993. 2016 Nov;128:82-91. doi: 10.1016/j.radphyschem.2016.06.003. Epub 2016 Jun 7.
7
Mechanistic Studies on RNA Strand Scission from a C2'-Radical.C2'-自由基引发的 RNA 链断裂的机制研究
J Org Chem. 2016 Oct 7;81(19):9199-9205. doi: 10.1021/acs.joc.6b01760. Epub 2016 Sep 26.
本文引用的文献
1
Independent generation and reactivity of uridin-2'-yl radical.尿苷-2'-基自由基的独立生成与反应活性。
J Org Chem. 2014 Nov 7;79(21):10303-10. doi: 10.1021/jo501916r. Epub 2014 Oct 17.
2
Chemical probing of RNA with the hydroxyl radical at single-atom resolution.以单原子分辨率用羟自由基对RNA进行化学探测。
Nucleic Acids Res. 2014 Nov 10;42(20):12758-67. doi: 10.1093/nar/gku934. Epub 2014 Oct 13.
3
In vivo X-ray footprinting of pre-30S ribosomes reveals chaperone-dependent remodeling of late assembly intermediates.体内 X 射线足迹分析揭示了前 30S 核糖体在伴侣蛋白依赖下对晚期组装中间体的重塑。
Mol Cell. 2013 Nov 21;52(4):506-16. doi: 10.1016/j.molcel.2013.09.020. Epub 2013 Oct 24.
4
Cooperative tertiary interaction network guides RNA folding.协同三级相互作用网络指导 RNA 折叠。
Cell. 2012 Apr 13;149(2):348-57. doi: 10.1016/j.cell.2012.01.057.
5
Direct strand scission in double stranded RNA via a C5-pyrimidine radical.通过 C5-嘧啶自由基对双链 RNA 进行直接链断裂。
J Am Chem Soc. 2012 Feb 29;134(8):3917-24. doi: 10.1021/ja300044e. Epub 2012 Feb 15.
6
Product and mechanistic analysis of the reactivity of a C6-pyrimidine radical in RNA.C6-嘧啶碱基在 RNA 中反应活性的产物和机理分析。
J Am Chem Soc. 2011 Apr 6;133(13):5152-9. doi: 10.1021/ja200317w. Epub 2011 Mar 10.
7
Challenges in developing DNA and RNA biomarkers of inflammation.开发炎症的DNA和RNA生物标志物所面临的挑战。
Biomark Med. 2007 Aug;1(2):293-312. doi: 10.2217/17520363.1.2.293.
8
Direct strand scission from a nucleobase radical in RNA.RNA 中碱基自由基的直接链断裂。
J Am Chem Soc. 2010 Mar 24;132(11):3668-9. doi: 10.1021/ja100281x.
9
Footprinting protein-DNA complexes using the hydroxyl radical.利用羟自由基对蛋白质-DNA复合物进行足迹分析。
Nat Protoc. 2008;3(6):1092-1100. doi: 10.1038/nprot.2008.72.
10
Nucleic acid oxidation in Alzheimer disease.阿尔茨海默病中的核酸氧化
Free Radic Biol Med. 2008 Apr 15;44(8):1493-505. doi: 10.1016/j.freeradbiomed.2008.01.002. Epub 2008 Jan 18.
Zotero 插件