Faculty of Pharmaceutical Sciences , Tokyo University of Science , 2641 Yamazaki , Noda , Chiba 278-8510 , Japan.
Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences , Tokyo Medical and Dental University , 1-5-45 Yushima , Bunkyo-ku , Tokyo 113-8519 , Japan.
J Org Chem. 2019 Jun 21;84(12):7971-7983. doi: 10.1021/acs.joc.9b00658. Epub 2019 Jun 6.
In this paper, we describe the first stereocontrolled synthesis and properties of boranophosphate DNA (PB-DNA), which contains all of the four nucleobases longer than 10mer. Synthesis was accomplished via an oxazaphospholidine approach combined with acid-labile protecting groups on nucleobases. It was demonstrated that there were significant differences between all-( Rp)- and all-( Sp)-PB-DNA in terms of the duplex-formation ability, nuclease resistance, and ribonuclease H (RNase H) activity. In particular, all-( Sp)-PB-DNA was demonstrated to show a duplex-formation ability with RNA and RNase H activity, both of which are necessary for antisense-type nucleic acid therapeutics.
本文描述了首例具有立体选择性的硼磷酸盐 DNA（PB-DNA）的合成及性质，其中包含所有长度超过 10 个碱基的四种碱基。该合成方法通过噁唑磷杂环戊烷方法结合碱基的酸不稳定保护基团来实现。结果表明，在双链体形成能力、核酸酶抗性和核糖核酸酶 H（RNase H）活性方面，全（Rp）-和全（Sp）-PB-DNA 之间存在显著差异。特别是，全（Sp）-PB-DNA 被证明与 RNA 形成双链体并具有 RNase H 活性，这两者都是反义型核酸治疗所必需的。
