Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan; Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, 11884 Cairo, Egypt.
Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira-ku, Sapporo 062-8517, Japan.
Bioorg Med Chem Lett. 2021 Sep 15;48:128257. doi: 10.1016/j.bmcl.2021.128257. Epub 2021 Jul 9.
The interstrand crosslinking of nucleic acids is one of the strategies to create the stable complex between an oligonucleotide and RNA by covalent bond formation. We previously reported that fully 2'-O-methylated (2'-OMe) RNAs having the 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. In this study, we established a chemical method to efficiently synthesize the crosslinked 2'-OMe RNA duplexes using AVP and prepared the anti-miRNA oligonucleotides (AMOs) containing the antisense targeting miR-21 and crosslinked duplex at the terminal sequences. These AMOs showed a markedly higher anti miRNA activity than that of the commercially-available miR-21 inhibitor which has locked nucleic acid (LNA) residues.
核酸链间交联是通过形成共价键在寡核苷酸和 RNA 之间创建稳定复合物的策略之一。我们之前报道过，具有 2-氨基-6-乙烯基嘌呤 (AVP) 的完全 2'-O-甲基化 (2'-OMe) RNA 能够有效地与靶 RNA 中的尿嘧啶发生交联。在这项研究中，我们建立了一种使用 AVP 高效合成交联 2'-OMe RNA 双链体的化学方法，并制备了在末端序列中含有反义靶向 miR-21 和交联双链体的抗 miRNA 寡核苷酸 (AMO)。这些 AMO 显示出比具有锁核酸 (LNA) 残基的市售 miR-21 抑制剂更高的抗 miRNA 活性。
