Synthesis and properties of thymidines with six-membered amide bridge

Yoshiyuki Hari; Takashi Osawa; Yutaro Kotobuki; Aiko Yahara; Ajaya R Shrestha; Satoshi Obika

doi:10.1016/j.bmc.2013.04.049

Synthesis and properties of thymidines with six-membered amide bridge

Bioorg Med Chem. 2013 Jul 15;21(14):4405-12. doi: 10.1016/j.bmc.2013.04.049. Epub 2013 Apr 27.

Authors

Yoshiyuki Hari¹, Takashi Osawa, Yutaro Kotobuki, Aiko Yahara, Ajaya R Shrestha, Satoshi Obika

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

PMID: 23685179
DOI: 10.1016/j.bmc.2013.04.049

Abstract

Artificial thymidine monomers possessing amide or N-methylamide bridges were designed, synthesized, and introduced into oligonucleotides. UV-melting experiments showed that these oligonucleotides preferred single-stranded RNA (ssRNA) to single-stranded DNA (ssDNA) in duplex formation. Both amide- and N-methylamide-modified oligonucleotides led to a significant increase in the binding affinity to ssRNA by up to +4.7 and +3.7°C of the Tm value per modification, respectively, compared with natural oligonucleotide. In addition, their oligonucleotides showed high stability against 3'-exonuclease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemistry*
DNA / chemistry*
Drug Design*
Molecular Structure
RNA / chemistry*
Thymidine / chemical synthesis*
Thymidine / chemistry

Substances

Amides
RNA
DNA
Thymidine