Collateral Damage Occurs When Using Photosensitizer Probes to Detect or Modulate Nucleic Acid Modifications.
Collateral Damage Occurs When Using Photosensitizer Probes to Detect or Modulate Nucleic Acid Modifications.
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DOI：
10.1002/anie.202110649
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发表时间：
2022-02-07
期刊：
影响因子：
--
通讯作者：
Burrows CJ
中科院分区：
文献类型：
--
作者：
Fleming AM;Chabot MB;Nguyen NLB;Burrows CJ
核酸被化学修饰以微调其生物功能的性质。用于选择性标记碱基修饰的化学工具使新方法成为可能;光敏剂核黄素和蒽醌先前被提议选择性地氧化N6-甲基腺嘌呤（m6 A）或5-甲基胞嘧啶（5 mdC）。在本文中，允许核黄素、蒽醌或玫瑰红与规范核苷dA、dC、dG和dT以及修饰的碱基5 mdC、m6 A、8-氧代鸟嘌呤（dOG）和8-氧代腺嘌呤（dOA）反应，以对它们的反应性进行排名。核苷研究揭示，dOG是最具反应性的，并且天然核苷dG与5 mdC或m6 A的反应性更高或相似; dG与5 mdC或6 mdA在单链和双链DNA中对氧化剂的竞争证实了dG被有利地氧化。因此，光敏剂是具有差的化学选择性的混杂核酸氧化剂，其将负面影响细胞中修饰的核苷酸的靶向氧化的尝试。DNA/RNA的修饰影响它们的性质，包括对氧化的敏感性。5-甲基胞嘧啶和N6-甲基腺嘌呤竞争光氧化核黄素，蒽醌，或虎红对DNA中的dA，dG，dC和dT。这证实了dG更容易氧化，代表了在光敏探测碱基甲基化过程中的附带损伤。
Nucleic acids are chemically modified to fine-tune their properties for biological function. Chemical tools for selective tagging of base modifications enables new approaches; the photosensitizers riboflavin and anthraquinone were previously proposed to oxidize N6-methyladenine (m6A) or 5-methylcytosine (5mdC) selectively. Herein, riboflavin, anthraquinone, or Rose Bengal were allowed to react with the canonical nucleosides dA, dC, dG, and dT, and the modified bases 5mdC, m6A, 8-oxoguanine (dOG), and 8-oxoadenine (dOA) to rank their reactivities. The nucleoside studies reveal that dOG is the most reactive and that the native nucleoside dG is higher or similar in reactivity to 5mdC or m6A; competition in both single- and double-stranded DNA of dG vs. 5mdC or 6mdA for oxidant confirmed that dG is favorably oxidized. Thus, photosensitizers are promiscuous nucleic acid oxidants with poor chemoselectivity that will negatively impact attempts at targeted oxidation of modified nucleotides in cells. Modification of DNA/RNA impact their properties including susceptibility to oxidation. 5-Methylcytosine and N6-methyladenine were competed for photooxidation by riboflavin, anthraquinone, or Rose Bengal against dA, dG, dC, and dT in DNA. This confirmed dG is more oxidation prone, representing collateral damage during photosensitized probing for the base methylations.
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DOI：
10.1002/wrna.1586
发表时间：
2020-07
期刊：
Wiley interdisciplinary reviews. RNA
影响因子：
--
作者：
Jones JD;Monroe J;Koutmou KS
通讯作者：
Koutmou KS
DOI：
10.1016/j.jphotobiol.2004.09.009
发表时间：
2005-01-14
影响因子：
5.4
作者：
Montoya, SCN;Comini, LR;Cabrera, JL
通讯作者：
Cabrera, JL
DOI：
10.1002/anie.202110649
发表时间：
2022-02-07
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Fleming AM;Chabot MB;Nguyen NLB;Burrows CJ
通讯作者：
Burrows CJ
影响因子：
62.1
作者：
Genereux JC;Barton JK
通讯作者：
Barton JK
影响因子：
16.8
作者：
Jaffrey SR
通讯作者：
Jaffrey SR