Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides. Keywords: artificial nucleic acid; duplex-forming ability; oligonucleotide synthesis; Introduction The efficacy and safety of therapeutic oligonucleotides can be controlled by chemical modifications

• . For applications in antisense technology, chemical modifications aimed at enhancing the duplex-forming ability toward a target RNA (i.e., a complementary single-stranded RNA) and improving the stability against enzymatic degradations are commonly utilized. For instance, antisense oligonucleotides

• moiety (GuNA[Me]-T; Figure 1) [20]. The GuNA[Me]-T exhibited a similar duplex-forming ability and nuclease resistance as GuNA[H]-T. Since a subtle change in the structure of the 2',4'-BNA/LNA modulated its biophysical and pharmacological properties, in vivo experiments with GuNA[H] and GuNA[Me] are