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2′,4′‐BNA/LNA with 9‐(2‐Aminoethoxy)‐1,3‐diaza‐2‐oxophenoxazine Efficiently Forms Duplexes and Has Enhanced Enzymatic Resistance **
Author(s) -
Kishimoto Yuki,
Nakagawa Osamu,
Fujii Akane,
Yoshioka Kotaro,
Nagata Tetsuya,
Yokota Takanori,
Hari Yoshiyuki,
Obika Satoshi
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003982
Subject(s) - nucleic acid , nuclease , locked nucleic acid , chemistry , dna , stereochemistry , exonuclease , complementary dna , rna , biochemistry , oligonucleotide , combinatorial chemistry , polymerase , gene
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.