New base pairing motifs. The synthesis and thermal stability of oligodeoxynucleotides containing imidazopyridopyrimidine nucleosides with the ability to form four hydrogen bonds
New base pairing motifs. The synthesis and thermal stability of oligodeoxynucleotides containing imidazopyridopyrimidine nucleosides with the ability to form four hydrogen bonds
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DOI：
10.1021/ja0347686
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发表时间：
2003-08-20
影响因子：
15
通讯作者：
Matsuda, A
中科院分区：
文献类型：
--
作者：
Minakawa, N;Kojima, N;Matsuda, A
以咪唑并[5 '，4'：4，5]吡啶并[2，3 - 4]嘧啶核苷1-4（分别为N-N、O-O、N-O和O-N）为碱基对，设计合成了两组新的碱基对，并对其热稳定性进行了研究。通过5-碘咪唑核苷与适当的5-锡基嘧啶衍生物的Stille偶联反应，然后通过分子内环化合成了所提出的四个三环核苷1-4。将这些核苷掺入ODNs中以研究氢键结合能力。当一个分子的三环核苷掺入到每个ODN的中心（ODN I和II，每个17聚体），没有观察到明显的碱基配对特异性，并且所有双链体的稳定性低于含有天然G：C和A：T对的双链体。另一方面，当三个分子的三环核苷连续掺入到每个ODN（ODN III和IV，每个17聚体）的中心，由于特定的碱基配对的双链体的热和热力学稳定性进行了观察。含有NO：ON对的双链体的熔解温度（Tm）最高，为84.0 ℃，比含有G：C和A：T对的双链体分别高18.2和23.5 ℃。这一结果表明，NO和ON形成碱基对与四个H-键时，它们被纳入ODN。双链体含有NO：ON对显着稳定的援助的堆积能力的咪唑并吡喃嘧啶基地。因此，我们开发了一种热稳定的新的碱基配对基序，这应该是有用的稳定和调节的各种DNA结构。
The synthesis and thermal stability of oligodeoxynucleotides (ODNs) containing imidazo[5',4': 4,5]pyrido[2,3-4pyrimidine nucleosides 1-4 (N-N, O-O, N-O, and O-N, respectively) with the aim of developing two sets of new base pairing motifs consisting of four hydrogen bonds (H-bonds) is described. The proposed four tricyclic nucleosides 1-4 were synthesized through the Stille coupling reaction of a 5-iodoimidazole nucleoside with an appropriate 5-stannylpyrimidine derivative, followed by an intramolecular cyclization. These nucleosides were incorporated into ODNs to investigate the H-bonding ability. When one molecule of the tricyclic nucleosides was incorporated into the center of each ODN (ODN I and II, each 17mer), no apparent specificity of base pairing was observed, and all duplexes were less stable than the duplexes containing natural G:C and A:T pairs. On the other hand, when three molecules of the tricyclic nucleosides were consecutively incorporated into the center of each ODN (ODN III and IV, each 17mer), thermal and thermodynamic stabilization of the duplexes due to the specific base pairings was observed. The melting temperature (T-m) of the duplex containing the NO:ON pairs showed the highest T-m of 84.0 degreesC, which was 18.2 and 23.5 degreesC higher than that of the duplexes containing G:C and A:T pairs, respectively. This result implies that NO and ON form base pairs with four H-bonds when they are incorporated into ODNs. The duplex containing NO:ON pairs was markedly stabilized by the assistance of the stacking ability of the imidazopyriclopyrimidine bases. Thus, we developed a thermally stable new base pairing motif, which should be useful for the stabilization and regulation of a variety of DNA structures.