Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Chem Asian J. 2011 Oct 4;6(10):2747-52. doi: 10.1002/asia.201100229. Epub 2011 Sep 2.
DNA molecules are known to be important materials in sensing, aptamer selection, nanocomputing, and construction of unique architectures. The incorporation of modified nucleobases affords unique DNA properties for applications in areas that would otherwise be difficult or not possible. Earlier, we demonstrated that the boronic acid moiety can be introduced into DNA through polymerase-catalyzed reactions. In order to study whether such incorporation by polymerase is a general phenomenon, we designed and synthesized four boronic acid-modified thymidine triphosphate (TTP) analogues. The synthesis of certain analogues was through the use of a single dialkyne tether for both the Sonogashira coupling with thymidine and the later Cu-mediated [3+2] cycloaddition for linking the boronic acid moiety. This approach is much more efficient than the previously described method, and paves the way for the preparation of a large number of boronic acid-modified TTPs with a diverse set of structural features. All analogues showed very good stability under polymerase chain reaction (PCR) conditions and were recognized as a substrate by DNA polymerase, and thus incorporated into DNA.
DNA 分子是已知的重要物质，在传感、适体选择、纳米计算和独特结构的构建中都有应用。修饰碱基的掺入赋予了 DNA 独特的性质，使其能够应用于原本难以实现或不可能实现的领域。我们之前已经证明，硼酸部分可以通过聚合酶催化反应引入 DNA 中。为了研究聚合酶的这种掺入是否是一种普遍现象，我们设计并合成了四种硼酸修饰的胸苷三磷酸 (TTP) 类似物。某些类似物的合成是通过使用单个二炔基将胸腺嘧啶的 Sonogashira 偶联和随后的 Cu 介导的 [3+2] 环加成连接硼酸部分。这种方法比之前描述的方法效率更高，为制备具有多种结构特征的大量硼酸修饰的 TTP 铺平了道路。所有类似物在聚合酶链反应 (PCR) 条件下都表现出非常好的稳定性，并且被 DNA 聚合酶识别为底物，从而被掺入 DNA 中。
