Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, <Nagoya, 464-8603, Japan.
Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan.
Chem Asian J. 2020 Apr 17;15(8):1266-1271. doi: 10.1002/asia.201901728. Epub 2020 Feb 17.
Serinol nucleic acid (SNA) is a promising candidate for nucleic acid-based molecular probes and drugs due to its high affinity for RNA. Our previous work revealed that incorporation of 2,6-diaminpurine (D), which can form three hydrogen bonds with uracil, into SNA increases the melting temperature of SNA-RNA duplexes. However, D incorporation into short self-complementary regions of SNA promoted self-dimerization and hindered hybridization with RNA. Here we synthesized a SNA monomer of 2-thiouracil (sU), which was expected to inhibit base pairing with D by steric hindrance between sulfur and the amino group. To prepare the SNA containing D and sU in high yield, we customized the protecting groups on D and sU monomers that can be readily deprotected under acidic conditions. Incorporation of D and sU into SNA facilitated stable duplex formation with target RNA by suppressing the self-hybridization of SNA and increasing the stability of the heteroduplex of SNA and its complementary RNA. Our results have important implications for the development of SNA-based probes and nucleic acid drugs.
丝氨酰核酸（SNA）是一种很有前途的基于核酸的分子探针和药物候选物，因为它与 RNA 具有很高的亲和力。我们之前的工作表明，将可以与尿嘧啶形成三个氢键的 2,6-二氨基嘌呤（D）掺入 SNA 中会增加 SNA-RNA 双链体的熔点。然而，D 掺入 SNA 的短自身互补区域会促进自身二聚化，并阻碍与 RNA 的杂交。在这里，我们合成了 2-硫代尿嘧啶（sU）的 SNA 单体，预计硫和氨基之间的空间位阻会抑制与 D 的碱基配对。为了以高产率制备含有 D 和 sU 的 SNA，我们定制了 D 和 sU 单体上的保护基团，这些基团可以在酸性条件下很容易地脱保护。D 和 sU 的掺入通过抑制 SNA 的自身杂交并增加 SNA 与其互补 RNA 的异源双链体的稳定性，促进了与靶 RNA 的稳定双链体形成。我们的研究结果对基于 SNA 的探针和核酸药物的发展具有重要意义。
