GENERALIZED TRIPLEX FORMATION USING NUCLEOSIDE ANALOGUES

使用核苷类似物形成广义三链体

• 批准号: 6199033
• 负责人: LARRY W MCLAUGHLIN
• 金额: $ 26.42万
• 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/6199033
• 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(逐字摘自申请人的摘要)：我们建议开发一种 脱氧核糖核酸双链核酸靶向的全新方法。在 建议的识别复合体，DNA的靶向链插入自身 在双链的两个Watson-Crick面之间产生一种新型DNA 三联体。这些三联体被命名为雅努斯·韦奇三联体，以罗马神的名字命名。 亚努斯。Janus Wedge螺旋中的靶向Janus Wedge(JW)残基包含 两个氢键面，这样在插入DNA双链后， Janus楔形残基与目标的两个Watson-Crick面形成氢键 碱基对。最终的三链复合体包含更多 比目标Watson-Crick DNA双链更容易形成链间氢键。 我们将研究Janus的嘧啶和嘌呤类似物 楔形残留物。初步研究将集中在Janus Wedge的性质上 三联体--没有相互竞争的沃森-克里克相互作用形成的那些。 随后，我们将重点介绍必要的链入侵过程 以允许靶向双链DNA。在这方面，肽核 酸性(PNA)低聚物，其他具有中性主链的低聚物，选择性系留 配体，以及DNA呼吸的过程都可能对链有价值 入侵过程。 本研究的结果将为靶向研究提供新的途径。 双链DNA，一种可用于嘌呤-嘧啶和 嘧啶和嘌呤碱基对相等。它将概括出 序列识别基本上包括任何DNA序列。