journal article

Journal Article

Text

Journal of Organic Chemistry. 2024, 89(1), p. 269-280

Synthesis, Duplex-Forming Ability, and Enzymatic Stability of Oligonucleotides Modified with Amide-Linked Dinucleotides Containing a 3′,4′-Tetrahydropyran-Bridged Nucleic Acid

American Chemical Society

English

Text

2024-01-05

https://doi.org/10.1021/acs.joc.3c02019

Osawa T., Akino T., Obika S.. Synthesis, Duplex-Forming Ability, and Enzymatic Stability of Oligonucleotides Modified with Amide-Linked Dinucleotides Containing a 3′,4′-Tetrahydropyran-Bridged Nucleic Acid. Journal of Organic Chemistry 89, 269 (2024); https://doi.org/10.1021/acs.joc.3c02019.

Replacement of a phosphodiester linkage with an amide linkage can improve the binding affinity of oligonucleotides to complementary RNA and their stability toward nucleases. In addition, restricting the conformation of the sugar moiety and the phosphate backbone in oligonucleotides effectively improves duplex stability. In this study, we designed amide-linked dinucleotides containing a 3′,4′-tetrahydropyran-bridged nucleic acid (3′,4′-tpBNA) with a constrained sugar conformation as well as a torsion angle ϵ. Phosphoramidites of the designed dinucleotides were synthesized and incorporated into oligonucleotides. Conformational analysis of the synthesized dinucleotides showed that the sugar conformation of the S-isomer of the amide-linked dinucleotide containing 3′,4′-tpBNA was N-type, which has the same conformation as that of the RNA duplex, while that of another R-isomer was S-type. Tm analysis indicated that the oligonucleotides containing the synthesized S-isomer showed RNA-selective hybridizing ability, although their duplex-forming ability was slightly inferior to that of natural oligonucleotides. Interestingly, the stability of the oligonucleotides toward endonucleases was significantly improved by modification with the two types of amide-linked dinucleotides developed in this study.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Organic Chemistry, © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.joc.3c02019.

93452

Synthesis, Duplex-Forming Ability, and Enzymatic Stability of Oligonucleotides Modified with Amide-Linked Dinucleotides Containing a 3′,4′-Tetrahydropyran-Bridged Nucleic Acid

American Chemical Society

English

2024-01-05

Journal of Organic Chemistry

89

1

269

280

https://doi.org/10.1021/acs.joc.3c02019

https://hdl.handle.net/11094/93452