Synthesis and properties of GuNA purine/pyrimidine nucleosides and oligonucleotides

Shinji Kumagai, Hiroaki Sawamoto, Tomo Takegawa-Araki, Yuuki Arai, Shuhei Yamakoshi, Katsuya Yamada, Tetsuya Ohta, Eiji Kawanishi, Naohiro Horie, Takao Yamaguchi, Satoshi Obika

Research output: Contribution to journalArticlepeer-review

Abstract

We recently designed guanidine-bridged nucleic acids (GuNA), and GuNA bearing a thymine (T) nucleobase was synthesized and successfully incorporated into oligonucleotides. The GuNA-T-modified oligonucleotides possessed high duplex-forming ability towards their complementary single-stranded RNAs and were highly stable against 3-exonuclease. Therefore, GuNA is a promissing artificial nucleic acid for therapeutic antisense oligonucleotides. We herein report the facile synthesis of GuNA phosphoramidites bearing adenine (A), guanine (G), and 5-methylcytosine (mC) nucleobases and a robust method for the preparation of GuNA-modified oligonucleotides, even with sequences having acid-sensitive purine nucleobases. Oligonucleotides modified with GuNA-A,-G, or-mC possessed high duplex-forming ability, similar to those modified with GuNA-T. Moreover, some of the GuNA-modified oligonucleotides were revealed to have high base discriminating ability compared with that of their natural counterparts. GuNA nucleosides exhibited no genotoxicity in bacterial reverse mutation assays. Thus, all GuNAs (GuNA-T,-A,-G, and-mC) are now available to be examined in therapeutic applications. This journal is

Original languageEnglish
Pages (from-to)9461-9472
Number of pages12
JournalOrganic and Biomolecular Chemistry
Volume18
Issue number46
DOIs
Publication statusPublished - Dec 14 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis and properties of GuNA purine/pyrimidine nucleosides and oligonucleotides'. Together they form a unique fingerprint.

Cite this