Photoinduced reductive repair of thymine glycol: Implications for excess electron transfer through DNA containing modified bases
Photoinduced reductive repair of thymine glycol: Implications for excess electron transfer through DNA containing modified bases
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DOI：
10.1021/ja061304
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发表时间：
2006-08-23
影响因子：
15
通讯作者：
Nishimoto, Sei-ichi
中科院分区：
文献类型：
--
作者：
Ito, Takeo;Kondo, Akiko;Nishimoto, Sei-ichi
以还原型黄素腺嘌呤二核苷酸（FADH（-））为分子间电子供体或以共价连接的吩噻嗪（PTZ）为分子内电子供体，研究了寡脱氧核苷酸中胸腺嘧啶乙二醇的光诱导还原反应。从光激发的黄素（*FADH（-））到游离的胸苷二醇的分子间电子捐赠产生高产量的胸苷，沿着少量的6-羟基-5，6-二氢胸苷。在光还原的情况下，4-mer长的单链寡脱氧核苷酸含有胸腺嘧啶乙二醇 *FADH-，胸腺嘧啶的恢复产率根据寡脱氧核苷酸的序列而变化。用时间分辨光谱法研究了激光激发的N，N-二甲基苯胺（DMA）光还原反应，结果表明，胸腺嘧啶二醇自由基阴离子上的一个氢氧根离子以10（4）s（-1）的速率被消除，生成6-羟基-5，6-二氢胸腺嘧啶（6-HOT）。作为关键中间体，随后进一步减少6-HOT。转化为胸苷或6-羟基-5，6-二氢胸腺嘧啶（6-HOT）。另一方面，注射到含有胸腺嘧啶乙二醇的双链DNA中的过量电子没有被捕获在损伤处，而是进一步沿双链体沿着运输。考虑到核碱基和PTZ的氧化还原性质，在嘧啶碱基（胸腺嘧啶，T和胞嘧啶，C）处的竞争性过量电子捕获导致自由基阴离子（T-，C-.）或快速背电子转移到PTZ的自由基阳离子（PTZ（+）），据推测比从DNA中胸腺嘧啶乙二醇的自由基阴离子中消除氢氧根离子更快。
Photoinduced reduction of thymine glycol in oligodeoxynucleotides was investigated using either a reduced form of flavin adenine dinucleotide (FADH(-)) as an intermolecular electron donor or covalently linked phenothiazine (PTZ) as an intramolecular electron donor. Intermolecular electron donation from photoexcited flavin (*FADH(-)) to free thymidine glycol generated thymidine in high yield, along with a small amount of 6-hydroxy-5,6-dihydrothymidine. In the case of photoreduction of 4-mer long single-stranded oligodeoxynucleotides containing thymine glycol by *FADH-, the restoration yield of thymine was varied depending on the sequence of oligodeoxynucleotides. Time-resolved spectroscopic study on the photoreduction by laser-excited N,N-dimethylaniline (DMA) suggested elimination of a hydroxyl ion from the radical anion of thymidine glycol with a rate constant of similar to 10(4)s(-1) generates 6-hydroxy-5,6-dihydrothymidine (6-HOT.) as a key intermediate, followed by further reduction of 6-HOT. to thymidine or 6-hydroxy-5,6-dihydrothymdine (6-HOT). On the other hand, an excess electron injected into double-stranded DNA containing thymine glycol was not trapped at the lesion but was further transported along the duplex. Considering redox properties of the nucleobases and PTZ, competitive excess electron trapping at pyrimidine bases (thymine, T and cytosine, C) which leads to protonation of the radical anion (T-., C-.) or rapid back electron transfer to the radical cation of PTZ (PTZ(+.)), is presumably faster than elimination of the hydroxyl ion from the radical anion of thymine glycol in DNA.