Institut für Organische Chemie, Universität Stuttgart, 70569, Stuttgart, Germany.
Chemistry. 2021 Nov 17;27(64):15918-15921. doi: 10.1002/chem.202102996. Epub 2021 Oct 8.
High fidelity base pairing is important for the transmission of genetic information. Weak base pairs can lower fidelity, complicating sequencing, amplification and replication of DNA. Thymidine 5'-monophosphate (TMP) is the most weakly pairing nucleotide among the canonical deoxynucleotides, causing high errors rates in enzyme-free primer extension. Here we report the synthesis of an ethynylpyridone C-nucleoside analog of 3'-amino-2',3'-dideoxythymidine monophosphate and its incorporation in a growing strand by enzyme-free primer extension. The ethynylpyridone C-nucleotide accelerates extension more than five-fold, reduces misincorporation and readily displaces TMP in competition experiments. The results bode well for the use of the C-nucleoside as replacements for thymidine in practical applications.
高保真碱基配对对于遗传信息的传递很重要。弱碱基对会降低保真度，使 DNA 的测序、扩增和复制变得复杂。胸苷 5'-单磷酸（TMP）是经典脱氧核苷酸中配对能力最弱的核苷酸，导致在无酶引物延伸过程中产生高错误率。本文报道了 3'-氨基-2'，3'-二脱氧胸苷单磷酸的乙炔基吡啶酮 C-核苷类似物的合成及其在无酶引物延伸过程中掺入正在延伸的链中。乙炔基吡啶酮 C-核苷酸可使延伸速度加快五倍以上，减少错配，并在竞争实验中容易取代 TMP。这些结果为在实际应用中用 C-核苷替代胸苷提供了良好的前景。
