DNAにおける5,6-ジヒドロピリミジンペロキシル基の反応性
Joanna Maria N San Pedro1, Marc M Greenberg
1Department of Chemistry, Johns Hopkins University , 3400 N. Charles St., Baltimore, Maryland 21218, United States.
Journal of the American Chemical Society
|March 4, 2014
まとめ
DNAの核塩基ラジカルは,鎖の断裂を直接引き起こしません. 代わりに,それらの過酸化ラジカルは隣接するグアニン基を損傷し,酸化によるDNA損傷につながる可能性があります.
科学分野:
- 分子生物学は分子生物学である.
- オキシダティブ・ストレスは,
- DNAの損傷と修復
背景:
- 核基根は,酸化ストレスによりDNAで形成される反応性種です.
- その形成と反応性を理解することは,DNA損傷メカニズムを理解するために極めて重要です.
研究 の 目的:
- 2つの特定の核塩基ラジカルの直接的なDNAダメージの可能性を調査する: 5-hydroxy-5,6-dihydrothymidin-6-ylラジカルと5,6-dihydrouridin-6-ylラジカル.
- オリゴヌクレオチド内のこれらのラジカルおよびそれらの派生ペロキシルラジカルの反応経路と製品を決定する.
主な方法:
- 核基根の光化学的前駆体を含むオリゴヌクレオチドの化学合成.
- 5-ヒドロキシ-5,6-ジヒドロチミジン-6-イル基と5,6-ジヒドロウリジン-6-イル基の生成.
- 様々なDNA配列を用いて,DNA鎖の断裂,アルカリ・ラビル病変,酸化的損傷産物の分析.
主要な成果:
- 核塩基根が直接誘発した鎖破裂や,単一鎖または二重鎖DNAのアルカリ・ラビル病変はありません.
- 核塩基ラジカルによって酸素を捕獲すると,好ましく5'-隣接するデオキシグアナシン (dG) 塩基に添加されるペロキシルラジカルが形成されます.
- ディスタルデオキシグアノシン (dG) 塩基も酸化的に損傷し,主に5'-隣接するdGの共振変異により,電子移転の証拠はありませんでした.
結論:
- 核塩基ラジカル自体は,DNA鎖の断裂やアルカリ・ラビル病変の直接的イニシアターではありません.
- 二次ペロキシルラジカルは,デオキシグアノシン (dG) 残基を標的とした酸化性DNA損傷の主要な媒介者です.
- 損傷の伝播は,電子移転機構ではなく,共振的修正を伴う.
さらに関連する動画
12:15Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
8.2K
13:41Monitoring Equilibrium Changes in RNA Structure by 'Peroxidative' and 'Oxidative' Hydroxyl Radical Footprinting
Published on: October 17, 2011
13.5K
関連する概念動画
01:11Radical Reactivity: Overview
2.2K
Radicals, the highly reactive species, gain stability by undergoing three different reactions. The first reaction involves a radical-radical coupling, in which a radical combines with another radical, forming a spin‐paired molecule. The second reaction is between a radical and a spin‐paired molecule, generating a new radical and a new spin‐paired molecule. The third reaction is radical decomposition in a unimolecular reaction, forming a new radical and a spin‐paired...
2.2K
01:02Radical Reactivity: Electrophilic Radicals
1.6K
Radicals adjacent to electron‐withdrawing groups are called electrophilic radicals. These radicals readily react with nucleophilic alkenes. For example, the malonate radical, in which the radical center is flanked by two electron‐withdrawing groups, reacts readily with butyl vinyl ether, which consists of an electron‐donating oxygen substituent. The reaction between electrophilic malonate radical and nucleophilic vinyl ether is favored because the radical has a...
1.6K
00:51Radical Formation: Elimination
1.6K
Another method of radical formation is the elimination process. It is the opposite of the addition route and is driven by the instability of the radical. For example, as depicted in Figure 1, dibenzoyl peroxide yields a pair of unstable radicals upon homolysis. Given its instability, this radical spontaneously undergoes elimination via a C–C bond cleavage to form a relatively more stable phenyl radical. The mechanism involves cleavage of the bond between the α and β positions...
1.6K
02:25Overview of DNA Repair
28.9K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
28.9K
01:10Radical Reactivity: Steric Effects
1.6K
The presence of electron-donating, electron-withdrawing, or conjugating groups adjacent to a radical center, imparts electronic stabilization to the radicals. Examples of such electronically-stabilized radicals are triphenylmethyl, tetramethylpiperidine‐N‐oxide, and 2,2‐diphenyl‐1‐picrylhydrazyl. These radicals are remarkably stable and are known as persistent radicals. Some of the persistent radicals can even be isolated and purified.
Along with electronic...
Along with electronic...
1.6K
01:20Radical Autoxidation
2.5K
The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
2.5K