Diafa Stella, Evéquoz Damien, Leumann Christian J, Hollenstein Marcel
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012, Bern, Switzerland.
Department of Structural Biology and Chemistry, Institut Pasteur, CNRS UMR3523, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France.
Chem Asian J. 2017 Jun 19;12(12):1347-1352. doi: 10.1002/asia.201700374. Epub 2017 Apr 24.
The selection of artificial genetic polymers with tailor-made properties for their application in synthetic biology requires the exploration of new nucleosidic scaffolds that can be used in selection experiments. Herein, we describe the synthesis of a bicyclo-DNA triphosphate (i.e., 7',5'-bc-TTP) and show its potential to serve for the generation of new xenonucleic acids (XNAs) based on this scaffold. 7',5'-bc-TTP is a good substrate for Therminator DNA polymerase, and up to seven modified units can be incorporated into a growing DNA chain. In addition, this scaffold sustains XNA-dependent DNA synthesis and potentially also XNA-dependent XNA synthesis. However, DNA-dependent XNA synthesis on longer templates is hampered by competitive misincorporation of deoxyadenosine triphosphate (dATP) caused by the slow rate of incorporation of 7',5'-bc-TTP.
为了在合成生物学中应用而选择具有定制特性的人工遗传聚合物，需要探索可用于筛选实验的新核苷支架。在此，我们描述了一种双环-DNA三磷酸（即7',5'-bc-TTP）的合成，并展示了其基于该支架生成新的异核酸（XNA）的潜力。7',5'-bc-TTP是Therminator DNA聚合酶的良好底物，并且多达七个修饰单元可以掺入到正在生长的DNA链中。此外，该支架支持XNA依赖性DNA合成，并且可能还支持XNA依赖性XNA合成。然而，由于7',5'-bc-TTP掺入速率缓慢导致脱氧腺苷三磷酸（dATP）的竞争性错误掺入，阻碍了在较长模板上进行DNA依赖性XNA合成。
