Issue 56, 2020
From the journal:

RSC Advances

Synthesis and properties of DNA oligomers containing stereopure phosphorothioate linkages and C-5 modified deoxyuridine derivatives†

Rintaro Iwata Hara, ORCID logo ab   Reijiro Yoshino,a   Yohei Nukaga,a   Yusuke Maeda,a   Kazuki Satoa  and  Takeshi Wada ORCID logo *a  

* Corresponding authors

a Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
E-mail: twada@rs.tus.ac.jp

b Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-Ku, Tokyo, Japan

Abstract

Phosphorothioate (PS) modification, where a non-bridging oxygen atom in a phosphodiester linkage is replaced by a sulfur atom, is widely used to improve the properties of nucleic acid drugs. Each PS linkage can be found in two stereoisomers, Rp and Sp. Since one non-bridging oxygen or sulfur atom in Sp-PS or Rp-PS, respectively, is located close to the C-5 substituent of uracil in a DNA/RNA hybrid duplex, the combination of the stereochemistry of the PS linkages and the type of the C-5 modification of uracil bases is expected to affect the properties of the hybrid duplexes. Herein, DNA oligomers containing both stereopure phosphorohioate linkages and C-5 modified deoxyuridine derivatives were synthesized. The thermodynamic stability of the DNA/RNA and DNA/DNA duplexes and RNase H activity of the DNA/RNA duplexes were evaluated. The combination of 5-propynyluracil and (Rp)-PS linkages in a DNA strand could significantly increase the thermal stability of a DNA/RNA hybrid duplex without reducing its RNase H activity.

Graphical abstract: Synthesis and properties of DNA oligomers containing stereopure phosphorothioate linkages and C-5 modified deoxyuridine derivatives

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Article information

DOI
https://doi.org/10.1039/D0RA06970A
Article type
Paper
Submitted
12 Jun 2020
Accepted
03 Sep 2020
First published
15 Sep 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 34006-34013

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Synthesis and properties of DNA oligomers containing stereopure phosphorothioate linkages and C-5 modified deoxyuridine derivatives

R. I. Hara, R. Yoshino, Y. Nukaga, Y. Maeda, K. Sato and T. Wada, RSC Adv., 2020, 10, 34006 DOI: 10.1039/D0RA06970A

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