Synthesis of 1′-phenyl-2′-OMe ribose analogues connecting the thymine base at the 1′ position through a flexible linker for the formation of a stable anti-parallel triplex DNA

Yosuke Taniguchi, Hidenori Okamura, Norihiko Fujino, Shigeki Sasaki

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6 Citations (Scopus)

Abstract

We have previously developed the innovative bicyclic nucleoside analogues (WNA) for the formation of the triplex DNA. The WNA analogue consists of an aromatic ring and a recognition base on the bicyclic skeleton, and the recognition of the CG or TA interrupting sites has been achieved by the WNA analogues. However, the stabilization ability of the WNA analogue is dependent on its neighboring nucleobases within the TFO. We hypothesized that the sequence dependency might arise from the fixed conformation of the bicyclic ring of the WNA. Thus, it was expected that an open-linker between the sugar part and the nucleobase might produce the flexibility and improve the stabilizing effect of the nucleobase analogues. We now report the design and synthesis of a new nucleoside analogue as an open-form of WNA-βT, the 1′-phenyl- 2′-OMe-ribose derivative, connecting the thymine base to the ribose part through a methylene linker (1) or an ethylene linker (2). TFO containing the 3′-dA-1-dG context recognized the CG interrupting site, and that with the 3′-dG-1-dG context recognized the GC site. In contrast, 2 displayed a stabilizing effect on all four base pairs with some preferences for the TFO containing 3′-dA-2-dG and 3′-dG-2-dG. These results suggested that a flexible linker between the nucleobase and the ribose part may improve the sequence dependency for the triplex formation.

Original languageEnglish
Pages (from-to)600-606
Number of pages7
JournalTetrahedron
Volume69
Issue number2
DOIs
Publication statusPublished - Jan 14 2013

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Thymine
Ribose
Nucleosides
Skeleton
Sugars
Base Pairing
Conformations
Stabilization
Derivatives
triplex DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

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title = "Synthesis of 1′-phenyl-2′-OMe ribose analogues connecting the thymine base at the 1′ position through a flexible linker for the formation of a stable anti-parallel triplex DNA",
abstract = "We have previously developed the innovative bicyclic nucleoside analogues (WNA) for the formation of the triplex DNA. The WNA analogue consists of an aromatic ring and a recognition base on the bicyclic skeleton, and the recognition of the CG or TA interrupting sites has been achieved by the WNA analogues. However, the stabilization ability of the WNA analogue is dependent on its neighboring nucleobases within the TFO. We hypothesized that the sequence dependency might arise from the fixed conformation of the bicyclic ring of the WNA. Thus, it was expected that an open-linker between the sugar part and the nucleobase might produce the flexibility and improve the stabilizing effect of the nucleobase analogues. We now report the design and synthesis of a new nucleoside analogue as an open-form of WNA-βT, the 1′-phenyl- 2′-OMe-ribose derivative, connecting the thymine base to the ribose part through a methylene linker (1) or an ethylene linker (2). TFO containing the 3′-dA-1-dG context recognized the CG interrupting site, and that with the 3′-dG-1-dG context recognized the GC site. In contrast, 2 displayed a stabilizing effect on all four base pairs with some preferences for the TFO containing 3′-dA-2-dG and 3′-dG-2-dG. These results suggested that a flexible linker between the nucleobase and the ribose part may improve the sequence dependency for the triplex formation.",
author = "Yosuke Taniguchi and Hidenori Okamura and Norihiko Fujino and Shigeki Sasaki",
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AU - Okamura, Hidenori

AU - Fujino, Norihiko

AU - Sasaki, Shigeki

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