GENERALIZED TRIPLEX FORMATION USING NUCLEOSIDE ANALOGS

DNA三螺旋的形成将通过系统的方式进行检查 开发各种碱基类似物以研究一系列碱基 三胞胎识别模体。例如，我们将研究八种不同的 靶向同型嘌呤序列的识别基序。这八个人 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，见下图)，(Ii)反平行- 链上的嘧啶-嘌呤-嘧啶基序，(Iii)反平行- 链状混合碱基，以及(Iv)平行链的嘧啶- 嘌呤-嘧啶基序。各种核苷类似物将制备为 以描述和研究每种类型的识别主题。 用两种反平行分子靶向作用于嘧啶-嘌呤碱基对 还将进行搁浅和平行搁浅的基地三胞胎。这个 嘌呤-嘧啶-嘌呤三联体基序GTA将由 检查各种N_2-氨基嘌呤类似物以及含有 附加的官能团，用于增强氢键/碱的能力 堆叠交互作用。黄精(Xn)将被研究为它的能力 形成相应的嘌呤-嘧啶-嘌呤三联体XnCG。其他嘧啶类化合物 或者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 调节三联体的形成。 这项研究的系统性，以及使用 特别设计的碱基类似物，应该提供重要的见解 各种三螺旋络合物的形成和稳定性， 并提供了一条通用化靶向双链的途径 DNA序列。

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.