Facile synthesis and fundamental properties of an N-methylguanidine-bridged nucleic acid (GuNA[NMe])

Organic & Biomolecular Chemistry
Naohiro HorieSatoshi Obika

Abstract

An N-methylguanidine-bridged nucleic acid (GuNA[NMe]), a guanidine-bridged nucleic acid (GuNA) bearing a methyl substituent at the bridge, was successfully synthesised and incorporated into oligonucleotides. By employing an acetyl protecting group, GuNA[NMe]-modified oligonucleotides bearing acid-sensitive purine nucleobases were successfully prepared. The obtained GuNA[NMe]-modified oligonucleotides exhibit excellent binding affinity towards the complementary single-stranded RNA and DNA. Furthermore, even a single GuNA[NMe] modification provides robust enzymatic stability, similar to that achieved by the well-established phosphorothioate backbone modification. These data indicate that such a GuNA[NMe] represents a valuable modification for the development of therapeutic oligonucleotides.

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Citations

Oct 7, 2020·Natural Product Reports·Roberto G S BerlinckIgor D Jurberg
Nov 13, 2020·Organic & Biomolecular Chemistry·Shinji KumagaiSatoshi Obika

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Methods Mentioned

BETA
antisense oligonucleotides
column chromatography

Software Mentioned

GuNA

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