2′, 4′‐BNA/LNA with 9‐(2‐Aminoethoxy)‐1, 3‐diaza‐2‐oxophenoxazine Efficiently Forms Duplexes and Has Enhanced Enzymatic Resistance. Issue 7 (21st December 2020)

• Record Type: Journal Article
• Authors: Kishimoto, Yuki; Nakagawa, Osamu; Fujii, Akane; Yoshioka, Kotaro; Nagata, Tetsuya; Yokota, Takanori; Hari, Yoshiyuki; Obika, Satoshi
• Is Part Of: Chemistry. Volume 27:Issue 7(2021)
• Page Start: 2427
• Page End: 2438
• Publication Date: 2020-12-21
• Subjects: bridged nucleic acids -- enzyme resistance -- nucleobases -- pi interactions -- synthesis design; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202003982
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Artificial nucleic acids are widely used in various technologies, such as nucleic acid therapeutics and DNA nanotechnologies requiring excellent duplex‐forming abilities and enhanced nuclease resistance. 2′‐ O, 4′‐ C ‐Methylene‐bridged nucleic acid/locked nucleic acid (2′, 4′‐BNA/LNA) with 1, 3‐diaza‐2‐oxophenoxazine (BNAP (B H )) was previously reported. Herein, a novel B H analogue, 2′, 4′‐BNA/LNA with 9‐(2‐aminoethoxy)‐1, 3‐diaza‐2‐oxophenoxazine (G‐clamp), named BNAP‐AEO (B AEO ), was designed. The B AEO nucleoside was successfully synthesized and incorporated into oligodeoxynucleotides (ODNs). ODNs containing B AEO possessed up to 10 4 ‐, 152‐, and 11‐fold higher binding affinities for complementary (c) RNA than those of ODNs containing 2′‐deoxycytidine (C ), 2′, 4′‐BNA/LNA with 5‐methylcytosine (L ), or 2′‐deoxyribonucleoside with G‐clamp (P AEO ), respectively. Moreover, duplexes formed by ODN bearing B AEO with cDNA and cRNA were thermally stable, even under molecular crowding conditions induced by the addition of polyethylene glycol. Furthermore, ODN bearing B AEO was more resistant to 3′‐exonuclease than ODNs with phosphorothioate linkages. Abstract : Stability by design : Artificial nucleic acids are widely used and in some applications require excellent duplex‐forming abilities and enhanced nuclease resistance. 2′‐ O, 4′‐ C ‐Methylene‐bridged nucleic acid/locked nucleic acid (2′, 4′‐BNA/LNA) with G‐clamp (BNAP‐AEO) is synthesized and incorporated into oligodeoxynucleotides (ODNs). These modified ODNs show high thermal stabilities toward complementary DNA and RNA.