Du Huang-Chi, Huang Hongbing
Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine , Houston, Texas 77030, United States.
Bioconjug Chem. 2017 Oct 18;28(10):2575-2580. doi: 10.1021/acs.bioconjchem.7b00416. Epub 2017 Sep 13.
DNA-encoded chemical libraries have emerged as a cost-effective alternative to high-throughput screening (HTS) for hit identification in drug discovery. A key factor for productive DNA-encoded libraries is the chemical diversity of the small molecule moiety attached to an encoding DNA oligomer. The library structure diversity is often limited to DNA-compatible chemical reactions in aqueous media. Herein, we describe a facile process for reducing aryl nitro groups to aryl amines. The new protocol offers simple operation and circumvents the pyrophoric potential of the conventional method (Raney nickel). The reaction is performed in aqueous solution and does not compromise DNA structural integrity. The utility of this method is demonstrated by the versatile synthesis of benzimidazoles on DNA.
DNA编码化学文库已成为药物发现中用于命中识别的高通量筛选（HTS）的一种经济高效的替代方法。高效DNA编码文库的一个关键因素是连接到编码DNA寡聚物上的小分子部分的化学多样性。文库结构多样性通常限于水性介质中与DNA兼容的化学反应。在此，我们描述了一种将芳基硝基还原为芳基胺的简便方法。新方案操作简单，避免了传统方法（雷尼镍）的自燃风险。该反应在水溶液中进行，不会损害DNA结构完整性。通过在DNA上通用合成苯并咪唑证明了该方法的实用性。
