Effects of halogenated WNA derivatives on sequence dependency for expansion of recognition sequences in non-natural-type triplexes

Yosuke Taniguchi, Ayako Nakamura, Yusuke Senko, Fumi Nagatsugi, Shigeki Sasaki

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-binding agents, but their target duplexes are limited to homopurine/homopyrimidine sequences because of interruption of the pyrimidines bases in the purine region. This problem has not been fully solved despite a wide variety of studies. Recently, we have developed a bicyclic system as a novel scaffold for nucleoside analogues (WNA, W-shaped nucleoside analogues) and determined two useful compounds, WNA-βT (2) and WNA-βC (5), for highly stable and selective triplex formation at a TA and a CG interrupting site, respectively. However, subsequent investigations have shown that the triplex formation using WNA is dependent on the neighboring bases of the TFOs. In this study, we have synthesized new WNA derivatives having halogenated recognition bases or benzene rings and evaluated the effects of the modifications on the triplex stability as well as selectivity. It has been found that the WNA-βT analogues holding 5-halogenated pyrimidine bases (WNA-βBrU (3) and WNA-βFU (4)) exhibit high CG-selectivity. On the other hand, the WNA-βT derivatives having the bromo-substituted benzene ring (mBr-WNA-βT (10) and oBr-WNA-βT (11)) have shown high selectivity to a TA interrupting site with high stability in the sequences to which the original WNA-βT do not bind. Thus, sequence-dependency has been overcome by the sequence-dependent use of WNA-βT, mBr-WNA-βT, and oBr-WNA-βT.

Original languageEnglish
Pages (from-to)2115-2122
Number of pages8
JournalJournal of Organic Chemistry
Volume71
Issue number5
DOIs
Publication statusPublished - Mar 5 2006

Fingerprint

Nucleosides
Derivatives
Benzene
Oligonucleotides
Pyrimidines
Scaffolds

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Effects of halogenated WNA derivatives on sequence dependency for expansion of recognition sequences in non-natural-type triplexes. / Taniguchi, Yosuke; Nakamura, Ayako; Senko, Yusuke; Nagatsugi, Fumi; Sasaki, Shigeki.

In: Journal of Organic Chemistry, Vol. 71, No. 5, 05.03.2006, p. 2115-2122.

Research output: Contribution to journalArticle

@article{f50249925f104410a49f26826e1f0cae,
title = "Effects of halogenated WNA derivatives on sequence dependency for expansion of recognition sequences in non-natural-type triplexes",
abstract = "Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-binding agents, but their target duplexes are limited to homopurine/homopyrimidine sequences because of interruption of the pyrimidines bases in the purine region. This problem has not been fully solved despite a wide variety of studies. Recently, we have developed a bicyclic system as a novel scaffold for nucleoside analogues (WNA, W-shaped nucleoside analogues) and determined two useful compounds, WNA-βT (2) and WNA-βC (5), for highly stable and selective triplex formation at a TA and a CG interrupting site, respectively. However, subsequent investigations have shown that the triplex formation using WNA is dependent on the neighboring bases of the TFOs. In this study, we have synthesized new WNA derivatives having halogenated recognition bases or benzene rings and evaluated the effects of the modifications on the triplex stability as well as selectivity. It has been found that the WNA-βT analogues holding 5-halogenated pyrimidine bases (WNA-βBrU (3) and WNA-βFU (4)) exhibit high CG-selectivity. On the other hand, the WNA-βT derivatives having the bromo-substituted benzene ring (mBr-WNA-βT (10) and oBr-WNA-βT (11)) have shown high selectivity to a TA interrupting site with high stability in the sequences to which the original WNA-βT do not bind. Thus, sequence-dependency has been overcome by the sequence-dependent use of WNA-βT, mBr-WNA-βT, and oBr-WNA-βT.",
author = "Yosuke Taniguchi and Ayako Nakamura and Yusuke Senko and Fumi Nagatsugi and Shigeki Sasaki",
year = "2006",
month = "3",
day = "5",
doi = "10.1021/jo052413u",
language = "English",
volume = "71",
pages = "2115--2122",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Effects of halogenated WNA derivatives on sequence dependency for expansion of recognition sequences in non-natural-type triplexes

AU - Taniguchi, Yosuke

AU - Nakamura, Ayako

AU - Senko, Yusuke

AU - Nagatsugi, Fumi

AU - Sasaki, Shigeki

PY - 2006/3/5

Y1 - 2006/3/5

N2 - Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-binding agents, but their target duplexes are limited to homopurine/homopyrimidine sequences because of interruption of the pyrimidines bases in the purine region. This problem has not been fully solved despite a wide variety of studies. Recently, we have developed a bicyclic system as a novel scaffold for nucleoside analogues (WNA, W-shaped nucleoside analogues) and determined two useful compounds, WNA-βT (2) and WNA-βC (5), for highly stable and selective triplex formation at a TA and a CG interrupting site, respectively. However, subsequent investigations have shown that the triplex formation using WNA is dependent on the neighboring bases of the TFOs. In this study, we have synthesized new WNA derivatives having halogenated recognition bases or benzene rings and evaluated the effects of the modifications on the triplex stability as well as selectivity. It has been found that the WNA-βT analogues holding 5-halogenated pyrimidine bases (WNA-βBrU (3) and WNA-βFU (4)) exhibit high CG-selectivity. On the other hand, the WNA-βT derivatives having the bromo-substituted benzene ring (mBr-WNA-βT (10) and oBr-WNA-βT (11)) have shown high selectivity to a TA interrupting site with high stability in the sequences to which the original WNA-βT do not bind. Thus, sequence-dependency has been overcome by the sequence-dependent use of WNA-βT, mBr-WNA-βT, and oBr-WNA-βT.

AB - Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-binding agents, but their target duplexes are limited to homopurine/homopyrimidine sequences because of interruption of the pyrimidines bases in the purine region. This problem has not been fully solved despite a wide variety of studies. Recently, we have developed a bicyclic system as a novel scaffold for nucleoside analogues (WNA, W-shaped nucleoside analogues) and determined two useful compounds, WNA-βT (2) and WNA-βC (5), for highly stable and selective triplex formation at a TA and a CG interrupting site, respectively. However, subsequent investigations have shown that the triplex formation using WNA is dependent on the neighboring bases of the TFOs. In this study, we have synthesized new WNA derivatives having halogenated recognition bases or benzene rings and evaluated the effects of the modifications on the triplex stability as well as selectivity. It has been found that the WNA-βT analogues holding 5-halogenated pyrimidine bases (WNA-βBrU (3) and WNA-βFU (4)) exhibit high CG-selectivity. On the other hand, the WNA-βT derivatives having the bromo-substituted benzene ring (mBr-WNA-βT (10) and oBr-WNA-βT (11)) have shown high selectivity to a TA interrupting site with high stability in the sequences to which the original WNA-βT do not bind. Thus, sequence-dependency has been overcome by the sequence-dependent use of WNA-βT, mBr-WNA-βT, and oBr-WNA-βT.

UR - http://www.scopus.com/inward/record.url?scp=33644643607&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644643607&partnerID=8YFLogxK

U2 - 10.1021/jo052413u

DO - 10.1021/jo052413u

M3 - Article

VL - 71

SP - 2115

EP - 2122

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 5

ER -