Synthesis of c-nucleosides designed to participate in triplex formation with native DNA:: Specific recognition of an A:T base pair in DNA
Synthesis of c-nucleosides designed to participate in triplex formation with native DNA:: Specific recognition of an A:T base pair in DNA
复制标题
DOI：
10.1021/jo0511445
复制
发表时间：
2005-10-28
影响因子：
3.6
通讯作者：
Gold, B
中科院分区：
文献类型：
--
作者：
Li, JS;Gold, B
我们之前已经描述了一个基于2-氨基喹啉和2-氨基喹唑啉的c -脱氧核苷（TRIPsides）系统，该系统被设计成可以通过Hoogsteen碱基配对与任何天然DNA序列特异性结合在主凹槽中的低聚物。根据它们结合的沃森-克里克碱基对靶标，这四种TRIPsides分别被称为antiGC、antig、antiTA和antiAT。前三个TRIPsides已经被制备，表征，并显示形成稳定的和序列特异性的三联体。在本研究中，我们描述了两种分子的制备，2-氨基-4-（2'-脱氧- β -d -核糖呋喃基）喹唑啉(7)和2-氨基-6-氟-4-（2'-脱氧- β -d -核糖呋喃基）喹啉（14），它们可以作为剩余的抗at TRIPside。制备了7和14的磷酰胺，但只有后者成功地结合到DNA低聚物中。使用紫外可见熔融实验证明，14在生理pH下形成具有A:T碱基对的序列特异性分子内三联体。
[GRAPHICS]We have previously described a system of 2-aminoquinoline- and 2-aminoquinazoline-based C-deoxynucleosides (TRIPsides) that are designed to be incorporated into oligomers that can specifically bind in the major groove via Hoogsteen base pairing to any sequence of native DNA. The four TRIPsides are termed antiGC, antiCG, antiTA, and antiAT with respect to the Watson-Crick base pair targets that they bind. The first three TRIPsides have been prepared, characterized, and shown to form stable and sequence-specific triplexes. In the present study, we describe the preparation of two molecules, 2-amino-4-(2'-deOXy-beta-D-ribofuranosyl)quinazoline (7) and 2-amino-6-fluoro-4-(2'-deoxy-beta-D-ribofuranosyl)quinoline (14), that can serve as the remaining antiAT TRIPside. The phosphoramidites of 7 and 14 were prepared, but only the latter was successfully incorporated into DNA oligomers. It is demonstrated using UV-visible melting experiments that 14 forms sequence-specific intramolecular triplets with A:T base pairs at physiological pH.