GENERALIZED TRIPLEX FORMATION USING NUCLEOSIDE ANALOGUES

使用核苷类似物形成广义三链体

• 批准号: 6519675
• 负责人: LARRY W MCLAUGHLIN
• 金额: $ 21.16万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6519675
• 关键词: DNA; chemical binding; conformation; hydrogen bond; intermolecular interaction; nucleic acid chemical synthesis; nucleic acid sequence; nucleic acid structure; nucleoside analog; triple helix

DESCRIPTION (Verbatim from the Applicant's abstract):We propose to develop a fundamentally new approach to nucleic acid targeting of DNA duplexes. In the proposed recognition complexes, the targeting strand of DNA inserts itself between the two Watson-Crick faces of the duplex to result in a new type of DNA triplex. These triplexes are termed Janus Wedge triplexes after the Roman god Janus. The targeting Janus Wedge (Jw) residue in the Janus Wedge helix contains two hydrogen bonding faces such that after insertion into the DNA duplex, the Janus Wedge residue is hydrogen bonded to both Watson-Crick faces of the target base pair. The final three-stranded complex contains significantly more interstrand hydrogen bonds than does the target Watson-Crick DNA duplex. We will examine both pyrimidine-like and purine-like analogues for the Janus Wedge residues. Initial studies will focus on the nature of the Janus Wedge triplex - those formed without competing Watson-Crick interactions. Subsequently we will focus on strand invasion processes that will be necessary to permit the targeting of duplex DNA. In this respect, the peptide nucleic acid (PNA) oligomers, other oligomers with neutral backbones, selected tethered ligands, and the process of DNA breathing may all be valuable to the strand invasion process. The results of this study will provide a new approach for the targeting of double-stranded DNA, one that can be used for both purine-pyrimidine and pyrimidine-purine base pairs equally. It will generalize the process of sequence recognition to include essentially any DNA sequence.

描述（来自申请人摘要的逐字）：我们提出开发一种 DNA双链体的核酸靶向的根本性新方法。在 提出的识别复合物，DNA的靶向链插入本身， 在双链体的两个沃森-克里克面之间产生一种新型的DNA 三层的这些三联体被称为雅努斯楔形三联体后，罗马神 杰纳斯Janus Wedge螺旋中的靶向Janus Wedge（Jw）残基含有 两个氢键面，使得插入DNA双链体后， Janus Wedge残基与靶的两个Watson-Crick面形成氢键 碱基对最后的三链复合体含有明显更多的 与靶沃森-克里克DNA双链体相比， 我们将研究Janus的嘧啶类和嘌呤类类似物 楔形残留物。最初的研究将集中在两面楔的性质 triplex -没有竞争性沃森-克里克相互作用形成的那些。 随后，我们将重点介绍链侵入过程，这将是必要的 以允许靶向双链体DNA。在这方面，肽核酸 酸（PNA）低聚物，具有中性主链的其它低聚物，选择的栓系的 配体和DNA呼吸的过程对DNA链来说都是有价值的 入侵过程 本研究的结果将为靶向 双链DNA，一种可以用于嘌呤-嘧啶和 嘧啶-嘌呤碱基对相等。它将概括出 序列识别基本上包括任何DNA序列。