2024-03-29T12:35:16Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00023847
2023-01-16T05:03:43Z
1903:1904:1905
Synthesis and Properties of 7-Deazapurine- and 8-Aza-7-deazapurine-Locked Nucleic Acid Analogues: Effect of the Glycosidic Torsion Angle
Hara, Takashi
70768
Kodama, Tetsuya
70769
Takegaki, Yumi
70770
Morihiro, Kunihiko
70771
Ito, Ramon Kosuke
70772
Obika, Satoshi
70773
Conformationally restricted nucleoside analogues 2′,4′-BNA/LNA-7-deazaguanine (LNA-7cG) and 2′,4′-BNA/LNA-8-aza-7-deazaguanine (LNA-8n7cG), which avoid extra hydrogen bond formation at the 7-position of the guanine nucleobase, were successfully synthesized and incorporated into oligonucleotides. While the LNA-7cG-containing oligonucleotides show high duplex-forming ability with complementary DNA and RNA similar to LNA-G, the LNA-8n7cG-containing oligonucleotide has lower binding affinity than that of natural 2′-deoxyguanosine. This disparity in thermostability is also observed in 7-deazaadenosine analogues (LNA-7cA, LNA-8n7cA). Thermodynamic parameters and computational chemistry revealed that an inappropriate glycosidic torsion angle χ of 2′,4′-BNA/LNA-8-aza-7-deazapurine analogues destabilizes duplex formation in contrast to 2′,4′-BNA/LNA-7-deazapurine analogues. This result indicates that the nucleobase rotation angle plays an important role in duplex binding affinity. In addition, LNA-7cG-modified oligonucleotide effectively suppresses aggregation even in a guanine-rich sequence.
journal article
ACS Publications
2016-12-13
application/pdf
Journal of Organic Chemistry
1
82
25
36
http://doi.org/10.1021/acs.joc.6b02525
http://hdl.handle.net/2237/26026
0022-3263
https://nagoya.repo.nii.ac.jp/record/23847/files/jo-2016-02525x_Revised_manuscript.pdf
eng
https://doi.org/10.1021/acs.joc.6b02525
“This document is the Accepted Manuscript version of a Published Work that appeared in final form in [Journal of Organic Chemistry], copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [<br/>http://pubs.acs.org/articlesonrequest/AOR-ydEFrgSbiWvtaGvc398M].”