8I50

Crystal structure of DNA octamer containing GuNA[Me,Me]

8I50 の概要

• エントリーDOI: 10.2210/pdb8i50/pdb
• 関連するPDBエントリー: 8HIS 8HU5
• 分子名称: DNA (5'-D(*GP*(OIQ)P*GP*(BRU)P*AP*CP*AP*C)-3') (2 entities in total)
• 機能のキーワード: dna, oligonucleotide, modified base
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2588.61

構造登録者

Aoyama, H.,Obika, S.,Yamaguchi, T. (登録日: 2023-01-21, 公開日: 2023-08-09, 最終更新日: 2023-09-06)

主引用文献

Yamaguchi, T.,Horie, N.,Aoyama, H.,Kumagai, S.,Obika, S.
Mechanism of the extremely high duplex-forming ability of oligonucleotides modified with N-tert-butylguanidine- or N-tert-butyl-N'- methylguanidine-bridged nucleic acids.
Nucleic Acids Res., 51:7749-7761, 2023

PubMed Abstract: Antisense oligonucleotides (ASOs) are becoming a promising class of drugs for treating various diseases. Over the past few decades, many modified nucleic acids have been developed for application to ASOs, aiming to enhance their duplex-forming ability toward cognate mRNA and improve their stability against enzymatic degradations. Modulating the sugar conformation of nucleic acids by substituting an electron-withdrawing group at the 2'-position or incorporating a 2',4'-bridging structure is a common approach for enhancing duplex-forming ability. Here, we report on incorporating an N-tert-butylguanidinium group at the 2',4'-bridging structure, which greatly enhances duplex-forming ability because of its interactions with the minor groove. Our results indicated that hydrophobic substituents fitting the grooves of duplexes also have great potential to increase duplex-forming ability.

PubMed: 37462081
DOI: 10.1093/nar/gkad608

実験手法

X-RAY DIFFRACTION (0.95 Å)