GENERALIZED TRIPLEX FORMATION USING NUCLEOSIDE ANALOGS

使用核苷类似物形成广义三链体

• 批准号: 2734776
• 负责人: LARRY W MCLAUGHLIN
• 金额: $ 16.84万
• 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 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734776
• 关键词: DNA; chemical binding; nucleic acid chemical synthesis; nucleic acid sequence; nucleic acid structure; nucleoside analog; triple helix

DNA triple helix formation will be examined in a systematic manner for by exploiting various base analogues in order to study a series of base triplet recognition motifs. For example, we will examine eight different recognition motifs for the targeting of homopurine sequences. These eight motifs include two motifs each of (i) the antiparallel-stranded purine- purine-pyrimidine motif (e.g., see graphic below), (ii) the antiparallel- stranded pyrimidine-purine-pyrimidine motif, (iii) the antiparallel- stranded mixed base motif, and (iv) the parallel-stranded pyrimidine- purine-pyrimidine motif. Various nucleoside analogues will be prepared as needed in order to characterize and study each type of recognition motif. The targeting of pyrimidine-purine base pairs using both antiparallel- stranded and parallel-stranded base triplets will also be undertaken. The purine-pyrimidine-purine triplet motif GTA will be further developed by examining various N2-aminopurine analogues, as well as those containing appended functionality, for their ability to enhance hydrogen bonding/base stacking interactions. Xanthosine (Xn) will be studied for its ability to form the related purine-pyrimidine-purine triplet XnCG. Other pyrimidines or smaller surrogate heterocycles will be functionalized to provide hydrogen bonding characteristics and then examined for their ability to mediate triplex formation. The systematic nature of this study, as well as the advantages of using specifically designed base analogues, should provide important insights into the formation and stability of a variety of triple helix complexes, and provide a route to the generalized targeting of double-stranded sequences of DNA.

DNA 三螺旋的形成将以系统的方式进行检查 利用各种碱基类似物来研究一系列碱基 三联体识别基序。例如，我们将检查八种不同的 用于靶向高嘌呤序列的识别基序。这八个 基序包括两个基序，每个基序为(i)反平行链嘌呤- 嘌呤-嘧啶基序（例如，参见下图），（ii）反平行- 链嘧啶-嘌呤-嘧啶基序，(iii) 反平行- 链混合碱基基序，以及（iv）平行链嘧啶- 嘌呤-嘧啶基序。各种核苷类似物将被制备为 需要为了表征和研究每种类型的识别主题。 使用反平行靶向嘧啶-嘌呤碱基对 还将进行绞链和平行链碱基三联体的研究。这 嘌呤-嘧啶-嘌呤三联体基序GTA将进一步开发 检查各种 N2-氨基嘌呤类似物，以及那些含有 附加功能，因为它们能够增强氢键/碱基 堆叠交互。将研究黄苷 (Xn) 的能力 形成相关的嘌呤-嘧啶-嘌呤三联体 XnCG。其他嘧啶类 或更小的替代杂环将被官能化以提供 氢键特性，然后检查它们的能力 介导三链体形成。 本研究的系​​统性以及使用的优点 专门设计的碱基类似物，应该提供重要的见解 影响各种三螺旋复合物的形成和稳定性， 并提供一条通用靶向双链的途径 DNA 序列。