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Synthesis and Properties of Oligonucleotides Containing 2′‐ O ,4′‐ C ‐Ethylene‐Bridged 5‐Methyluridine with Exocyclic Methylene and Methyl Groups in the Bridge
Author(s) -
Ito Yuta,
Nishida Kodai,
Tsutsui Norika,
Fuchi Yasufumi,
Hari Yoshiyuki
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100947
Subject(s) - chemistry , oligonucleotide , methylene , methylene bridge , stereochemistry , ethylene , nucleic acid , dna , nucleobase , methylene blue , duplex (building) , rna , medicinal chemistry , organic chemistry , biochemistry , gene , photocatalysis , catalysis
Novel 2′‐ O ,4′‐ C ‐ethylene‐bridged nucleic acid (ENA) analogs with exocyclic methylene and ( R )‐methyl groups at the 6′‐position were synthesized. The obtained 6′‐methylene‐ENA and 6′ R ‐Me‐ENA were incorporated into oligonucleotides, and their properties were compared with those of the corresponding natural, ENA‐, and 6′ S ‐Me‐ENA‐modified oligonucleotides. The duplex‐stabilizing ability of 6′‐methylene‐ENA and 6′ R ‐Me‐ENA with single‐stranded RNA (ssRNA) was similar to that of ENA and 6′ S ‐Me‐ENA under both dilute and molecular crowding conditions. On the other hand, oligonucleotides containing 6′‐methylene‐ENA and 6′ R ‐Me‐ENA formed stable triplexes with double‐stranded DNA (dsDNA) in comparison with those containing 6′ S ‐Me‐ENA. Their thermodynamic properties were also calculated to explore the influence of the substituents introduced at the 6′‐position of ENA. Moreover, oligonucleotides with ENA analogs exhibited excellent resistance against nucleases. These results suggest that 6′‐methylene‐ENA and 6′ R ‐Me‐ENA are promising candidates for targeting ssRNA and dsDNA.