Generation of DNA Interstrand Cross-Links by Post-Synthetic Reductive Amination
Generation of DNA Interstrand Cross-Links by Post-Synthetic Reductive Amination
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DOI：
10.1021/ol802719a
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发表时间：
2009-02-05
期刊：
影响因子：
5.2
通讯作者：
Schaerer, Orlando D.
中科院分区：
文献类型：
--
作者：
Angelov, Todor;Guainazzi, Angelo;Schaerer, Orlando D.
DNA链间交联（ICL）是许多抗肿瘤药物形成的临床上最相关的加合物。为了促进ICLs引发的生物学反应的研究，我们开发了一种新的方法来合成氮芥ICLs的模拟物。7-带有乙醛基团的脱氮鸟嘌呤残基被掺入DNA的互补链中，并通过双还原胺化诱导交联形成。我们的策略能够以高产率和纯度合成大沟交联。
DNA interstrand cross-links (ICLs) are the clinically most relevant adducts formed by many antitumor agents. To facilitate the study of biological responses triggered by ICLs, we developed a new approach toward the synthesis of mimics of nitrogen mustard ICLs. 7-Deazaguanine residues bearing acetaldehyde groups were incorporated into complementary strands of DNA and cross-link formation induced by double reductive amination. Our strategy enables the synthesis of major groove cross-links in high yields and purity.