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

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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

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All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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