Selective Formation of Stable Triplexes Including a TA or a CG Interrupting Site with New Bicyclic Nucleoside Analogues (WNA)
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- 作者：Shigeki Sasaki ; Yosuke Taniguchi ; Ryo Takahashi ; Yusuke Senko ; Keiichi Kodama ; Fumi Nagatsugi ; and Minoru Maeda
- 刊名：Journal of the American Chemical Society
- 出版年：2004
- 出版时间：January 21, 2004
- 年：2004
- 卷：126
- 期：2
- 页码：516 - 528
- 全文大小：383K
- 年卷期：v.126,no.2(January 21, 2004)
- ISSN：1520-5126
文摘
Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules and would becomepowerful tools for genomic research. As the stabilization of the TFO is partially provided by hydrogen bondsto purine bases, the most stable triplexes form with homopurine/homopyrimidine sequences, and a pyrimidinebase in the purine strand of the duplex interrupts triplex formation. If a TFO can recognize sequencesincluding such an interrupting site, the target regions in the genome would be expanded to a greater extent.However, this problem has not been generally solved despite extensive studies. We have previously reporteda new base analogue (WNA) constructed of three parts, a benzene ring, a heterocyclic ring, and a bicyclicskeleton to hold these two parts. In this study, we have further investigated modification of WNAsystematically and determined two useful WNA analogues, WNA-
T and WNA-C, for selective stabilizationof triplexes at a TA and a CG interrupting site, respectively. The triplexes with WNA analogues have exhibitedan interesting property in that they are more stable than natural-type triplexes even at low Mg2+ concentration.From comparison of the results with H-WNA-T lacking benzene and those with WNA-H without thymine,it has been suggested that benzene is a major contributor for triplex stability and thymine provides selectivity.Thus, it has been successfully demonstrated that WNA-T/TA and WNA-C/CG combinations may expandtriplex recognition codes in addition to the natural A/AT and G/GC base triplet codes. The results of thisstudy will provide useful information for the design of new WNA analogues to overcome inherent problemsfor further expansion of triplex recognition codes.
T and WNA-C, for selective stabilizationof triplexes at a TA and a CG interrupting site, respectively. The triplexes with WNA analogues have exhibitedan interesting property in that they are more stable than natural-type triplexes even at low Mg2+ concentration.From comparison of the results with H-WNA-T lacking benzene and those with WNA-H without thymine,it has been suggested that benzene is a major contributor for triplex stability and thymine provides selectivity.Thus, it has been successfully demonstrated that WNA-T/TA and WNA-C/CG combinations may expandtriplex recognition codes in addition to the natural A/AT and G/GC base triplet codes. The results of thisstudy will provide useful information for the design of new WNA analogues to overcome inherent problemsfor further expansion of triplex recognition codes.