Synthesis of new functionalized nucleic acids by the pentaerythritol linker.

通过季戊四醇接头合成新的功能化核酸。

• 批准号: 13470481
• 负责人: MATSUDA Akira
• 金额: $ 5.95万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470481/
• 关键词: pentaerythritol; antigene; triple helix; hydrogen bond; Hoogsteen; reverse Hoogsteen; thermal stability; foot printing; アントラキノン

The 3'-3'-linked oligodeoxynucleotides (ODNs) by pentaerythritol with an intercalator at the junction point is that can form the parallel triplexes with the duplex target by Hoogsteen hydrogen bonds were synthesized. Stability of the triplexes with the target duplexes was studied by thermal denaturation. The 3'-3'-linked ODNs with the anthraquinonyl group enhanced the thermal stability of the triplexes when compared with those without the intercalator and the unmodified nonamer. It was found that the ODNs carrying the anthraquinonyl groups can form thermally stable triplexes by skipping two or three extra base pairs between two binding domains of the target duplexes. The 3'-3'-linked ODN with the anthraquinonyl group at the junction point inhibited the cleavage by the enzyme Hind III more effectively.We also synthesized the 3'-3'-linked TFOs that can form the antiparallel triplexes with the duplex DNA target by reverse Hoogsteen hydrogen bonds. The alternate-strand triplexes were significantly stabilized by linking the TFO fragments with the pentaerythritol linker. And, unlike the alternate-strand triplexes composed of the pyrimidine motif, the terminal ammonium ion of the aminobutyl-linker and the intercalator of the TFOs did not contribute to the stability of the alternate-strand triplex comprised of the purine motif.

以季戊四醇为交联剂，在连接点处引入嵌入剂，合成了3 ′-3 ′-连接的寡脱氧核苷酸（ODNs），该寡脱氧核苷酸能与双链体靶分子通过Hoogsteen氢键形成平行的三链体。通过热变性研究具有靶双链体的三链体的稳定性。与没有嵌入剂和未修饰的九聚体相比，具有蒽醌基的3 '-3'-连接的ODNs增强了三链体的热稳定性。结果发现，携带蒽醌基的ODN可以通过跳过靶双链体的两个结合结构域之间的两个或三个额外碱基对而形成热稳定的三链体。我们还合成了3 '-3'-linked TFO，它们可以通过反向Hoogsteen氢键与双链体DNA靶形成反平行的三链体。交替链三链体通过将TFO片段与季戊四醇接头连接而显著稳定。并且，与由嘧啶基序组成的交替链三链体不同，氨基丁基接头的末端铵离子和TFO的嵌入剂对由嘌呤基序组成的交替链三链体的稳定性没有贡献。

项目成果

Ueno, Y., et al.: "Synthesis of the 3'-3'-linked oligonucleotides branched by the pentaerythritol linker and the thermal stabilities of the triplexes with the single stranded DNA or RNA"Bioconjugate Chem.. (in press).

Ueno, Y., 等人：“由季戊四醇接头分支的 3-3-连接寡核苷酸的合成以及具有单链 DNA 或 RNA 的三链体的热稳定性”Bioconjugate Chem..（出版中）。

Hoshika, S. et al.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides using a purine motif"Bioconjugate Chem.. (in press). (2002)

Hoshika, S. 等人：“使用嘌呤基序通过 3-3 连接的寡脱氧核苷酸形成交替链三螺旋”Bioconjugate Chem..（出版中）。

Ueno, Y., Mikawa, M., Hoshika, S., Matsuda, A.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point"Bioconjugate Chem.. 12. 635-642 (2001)

Ueno, Y.、Mikawa, M.、Hoshika, S.、Matsuda, A.：“3-3-连接的寡脱氧核苷酸与连接点上的蒽醌基团形成交替链三螺旋”Bioconjugate Chem。

Ueno, Y. Shibata, A., Matsuda, A, Kitade, Y.: "Synthesis of the 3'-3'-linked oligonucleotides branched by the pentaerythritol linker and the thermal stabilities of the triplexes with the single stranded DNA or RNA"Bioconjugate Chem.. in press.

Ueno, Y. Shibata, A.、Matsuda, A、Kitade, Y.：“季戊四醇接头分支的 3-3 连接寡核苷酸的合成以及单链 DNA 或 RNA 三链体的热稳定性”

Ueno, Y., et al.: "Alternate-stand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point"Nucleic Acids Res.. Suppl.1. 11-12 (2001)

Ueno, Y., et al.：“3-3-连接的寡脱氧核苷酸与连接点处的蒽醌基形成交替链三螺旋”Nucleic Acids Res.. Suppl.1。