Photoredox Deaminative Alkylation in DNA-Encoded Library Synthesis.
Photoredox Deaminative Alkylation in DNA-Encoded Library Synthesis.
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DOI：
10.1021/acs.orglett.2c00697
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发表时间：
2022-04
期刊：
影响因子：
5.2
通讯作者：
Yurong Shen;Guanyu Yang;Wei Huang;A. Shaginian;Qian Lin;Jinqiao Wan;Jin Li;Yun Deng;Guansai Liu
中科院分区：
文献类型：
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作者：
Yurong Shen;Guanyu Yang;Wei Huang;A. Shaginian;Qian Lin;Jinqiao Wan;Jin Li;Yun Deng;Guansai Liu
在此，我们报告了一种DNA光氧化还原介导的脱氨基烷基化方法，用于使具有胺衍生自由基的DNA标记的丙烯酰胺底物多样化。自由基可以方便地从空间位阻伯胺产生，并且脱氨基烷基化可以耐受广泛的自由基前体。此外，该方法适用于Boc-保护的二胺，游离氨基酸，和芳基卤化物，其带有官能团，使更多轮的多样化。该方法被认为提供了构建DNA编码文库的高潜力，如通过以2 × 3基质形式产生模拟文库以及通过UPLC-MS和qPCR实验确认DNA稳定性所证明的。
Herein, we report an on-DNA photoredox-mediated deaminative alkylation method for diversifying DNA-tagged acrylamide substrate with amine-derived radicals. The radicals can be conveniently generated from sterically hindered primary amines, and the deaminative alkylation can tolerate a broad array of radical precursors. Furthermore, the methodology is applicable to Boc-protected diamines, free amino acids, and aryl halides, which bear functional groups enabling additional rounds of diversification. The method is believed to offer a high potential for constructing DNA-encoded libraries, as was demonstrated by the production of a mock library in a 2 × 3 matrix format and confirmation of DNA stability by UPLC-MS and qPCR experiments.