Stable and Selective Formation of Hoogsteen-Type Triplexes and Duplexes Using Twisted Intercalating Nucleic Acids (TINA) Prepared via Postsynthetic Sonogashira Solid-Phase Coupling Reactions

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• 作者：Vyacheslav V. Filichev and Erik B. Pedersen
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：October 26, 2005
• 年：2005
• 卷：127
• 期：42
• 页码：14849 - 14858
• 全文大小：215K
• 年卷期：v.127,no.42(October 26, 2005)
• ISSN：1520-5126

文摘

Bulge insertions of (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol (5) into the middle ofhomopyrimidine oligodeoxynucleotides (twisted intercalating nucleic acids, TINA) obtained via postsyntheticSonogashira coupling reaction led to extraordinary high thermal stability of Hoogsteen-type triplexes andduplexes, whereas Watson-Crick-type duplexes of the same nucleotide content were destabilized. Modifiedoligonucleotides were synthesized using the phosphoramidite of (S)-1-(4,4'-dimethoxytriphenylmethyloxy)-3-(4-iodo-benzyloxy)-propan-2-ol followed by treatment of the oligonucleotide on a CPG-support with theSonogashira-coupling reaction mixture containing different ethynylaryls. Bulged insertion of the pyrenederivative 5 into oligonucleotides was found to be the best among the tested modifications for binding tothe Hoogsteen-type triplexes and duplexes. Thus, at pH 7.2 an oligonucleotide with cytidine content of36% possessing two bulged insertions of 5 separated by three bases formed a stable triplex (T_m = 43.0mages/entities/deg.gif">C), whereas the native oligonucleotide was unable to bind to the target duplex. The corresponding Watson-Crick-type duplex with the same oligonucleotide had T_m of 38.0 mages/entities/deg.gif">C at pH 7.2, while the T_m of unmodifieddsDNA was 47.0 mages/entities/deg.gif">C. Experiments with mismatched oligonucleotides, luminescent properties, and potentialapplications of TINA technology is discussed.