Development of antiparallel-type triplex-forming oligonucleotides containing quinoline derivatives capable of recognizing a T-A base pair in a DNA duplex

Shuhei Nishizawa; Gaohong Tu; Daisuke Ogata; Kouichiro Miyauchi; Akihiro Ohkubo

doi:10.1016/j.bmc.2022.116934

Development of antiparallel-type triplex-forming oligonucleotides containing quinoline derivatives capable of recognizing a T-A base pair in a DNA duplex

Bioorg Med Chem. 2022 Oct 1:71:116934. doi: 10.1016/j.bmc.2022.116934. Epub 2022 Jul 29.

Authors

Shuhei Nishizawa¹, Gaohong Tu¹, Daisuke Ogata¹, Kouichiro Miyauchi¹, Akihiro Ohkubo²

Affiliations

¹ Department of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama 226-8501, Japan.
² Department of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama 226-8501, Japan. Electronic address: aohkubo@bio.titech.ac.jp.

PMID: 35921784
DOI: 10.1016/j.bmc.2022.116934

Abstract

A triplex-forming oligonucleotide (TFO) can bind to genomic DNA and inhibit the expression of genes with specific sequences. However, to date, there have been a few reports of modified bases in antiparallel TFOs that can recognize and strongly bind to T-A base pairs. In this study, we introduced several quinoline derivatives into antiparallel TFOs to develop modified bases that can recognize the T-A base pair and evaluated their ability to form triplexes and to discriminate between base pairs. The introduction of 2-acetamido-6-aminoquinoline^6DAQ_ac) into an antiparallel TFO allowed the selective recognition of a T-A base pair at both low and high salt concentrations.

Keywords: DNA nanotechnology; Gene therapy; Modified oligonucleotide; Triplex-forming oligonucleotide.

Publication types

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

MeSH terms

Base Pairing
DNA* / metabolism
Molecular Structure
Nucleic Acid Conformation
Oligonucleotides*

Substances

Oligonucleotides
DNA