Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Miyagi, Japan.
Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aramaki Aza-Aoba, Aoba-ku, Sendai 980-8577, Miyagi, Japan.
Molecules. 2023 Feb 13;28(4):1766. doi: 10.3390/molecules28041766.
Synthetic unnatural base pairs have been proven to be attractive tools for the development of DNA-based biotechnology. Our group has very recently reported on alkynylated purine-pyridazine pairs, which exhibit selective and stable base-pairing via hydrogen bond formation between pseudo-nucleobases in the major groove of duplex DNA. In this study, we attempted to develop an on-column synthesis methodology of oligodeoxynucleotides (ODNs) containing alkynylated purine derivatives to systematically explore the relationship between the structure and the corresponding base-pairing ability. Through Sonogashira coupling of the ethynyl pseudo-nucleobases and CPG-bound ODNs containing 6-iodopurine, we have demonstrated the synthesis of the ODNs containing three Pu derivatives (Pu1, Pu2, Pu3) as well as three Pu derivatives (Pu1, Pu2, Pu3). The base-pairing properties of each alkynylated purine derivative revealed that the structures of pseudo-nucleobases influence the base pair stability and selectivity. Notably, we found that Pu1 bearing 2-pyrimidinone exhibits higher stability to the complementary Pz than the original Pu, thereby demonstrating the potential of the on-column strategy for convenient screening of the alkynylated purine derivatives with superior pairing ability.
人工合成的非天然碱基对已被证明是开发基于 DNA 的生物技术的有吸引力的工具。我们的小组最近报道了炔基嘌呤-哒嗪对，它们通过在 DNA 双螺旋的大沟中伪碱基之间形成氢键，表现出选择性和稳定的碱基配对。在这项研究中，我们试图开发一种含有炔基嘌呤衍生物的寡脱氧核苷酸（ODN）的柱上合成方法，以系统地探索结构与相应碱基配对能力之间的关系。通过乙炔基伪碱基与含有 6-碘嘌呤的 CPG 结合的 ODN 的 Sonogashira 偶联，我们已经证明了含有三个 Pu 衍生物（Pu1、Pu2、Pu3）以及三个 Pu 衍生物（Pu1、Pu2、Pu3）的 ODN 的合成。每个炔基嘌呤衍生物的碱基配对性质表明，伪碱基的结构影响碱基对的稳定性和选择性。值得注意的是，我们发现带有 2-嘧啶酮的 Pu1 对互补的 Pz 的稳定性高于原始 Pu，从而证明了柱上策略在方便筛选具有优越配对能力的炔基嘌呤衍生物方面的潜力。
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