Synthesis and properties of artificial nucleic acids utilizing pentaerythritol.

利用季戊四醇的人工核酸的合成和性质。

• 批准号: 16590082
• 负责人: UENO Yoshihito
• 金额: $ 2.3万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590082/
• 关键词: nucleoside; nucleotide; DNA; triplex; protein; linker; antigene method; 核酸; 三重鎖; 3'-3'結合型; 非対称; 塩基三量体; イノシン; キサントシン; ゲルシフト

First, the synthesis and thermal stabilities of the triplexes containing either 2'-deoxyinosine (1) or 2'-deoxyxanthosine (3) in their second strands were examined. It was found that the triplexes with the 2'-deoxy-5-methylcytidine(dM)・1:dC and dM・1:dA base triplets are thermally stable, but those containing the dM・1:T and dM・1:dG base triplets are unstable under both neutral and slightly acidic conditions. On the other hand, it was found that the oligonucleotide containing 3 could form thermally stable triplexes with the oligonucleotides that involve four natural bases opposite the sites of 3. The rank of the thermal stabilities of the triplexes was as follows : the triplex containing the dM・3:dC base triplet > that containing the dM・3:dA base triplet > that containing the dM・3:T base triplet > that containing the dM・3:dG base triplet.Furthermore, the synthesis of triplexes possessing an anthraquinonyl group and composed of branched oligonucleotides (ONs) was examined. Binding ability of a triplex-binding protein (MBP-LOR3^<ARF>) to the triplexes was evaluated by an electrophoretic mobility shift assay (EMSA). It was found that the triplex, which has an antraquinonecarbonyl group at the 5'-end of the third strand and is connected with the pentaerythritol linker, has greater affinity to the protein than an unmodified triplex.

首先，研究了含2'-脱氧肌苷(1)和2'-脱氧黄嘌呤(3)的三聚体的合成和热稳定性。结果发现，含有2'-脱氧-5-甲基胞苷（dM）·1:dC和dM·1:dA碱基三联体的三联体是热稳定的，但含有dM·1:T和dM·1:dG碱基三联体的三联体在中性和微酸性条件下都是不稳定的。另一方面，发现含有3的寡核苷酸可以与含有4个天然碱基的寡核苷酸形成热稳定的三联体。三联体的热稳定性排序如下：含有dM·3:dC基三重态的三联体>含有dM·3:dA基三重态>含有dM·3:T基三重态>含有dM·3:dG基三重态。此外，还研究了由支链寡核苷酸（ONs）组成的含蒽醌基三萜化合物的合成。三联体结合蛋白（MBP-LOR3^<ARF>）与三联体的结合能力通过电泳迁移转移试验（EMSA）评估。结果发现，在第三链5'端有一个蒽醌羰基并与季戊四醇连接的三联体比未修饰的三联体对蛋白质具有更大的亲和力。

项目成果

Alternate-strand triple-helix formation by 3'-3'-linked oligodeoxynucleotides composed of asymmetrical sequences

由不对称序列组成的 3-3-连接寡脱氧核苷酸形成交替链三螺旋

• 发表时间: 2004
• 期刊: Bioorg. Med. Chem. Lett. 14
• 作者: S.Hoshika;Y.Ueno;H.Kamiya;A.Matsuda
• 通讯作者: A.Matsuda

Alternate-strand triple-helix formation by 3'-3'-linked oligodeoxynucleotides composed of asymmetrical sequences.

由不对称序列组成的 3-3 连接寡脱氧核苷酸形成交替链三螺旋。

• 发表时间: 2004
• 期刊: Bioorg.Med.Chem.Lett. 14
• 作者: S.Hoshika;Y.Ueno;H.Kamiya;A.Matsuda
• 通讯作者: A.Matsuda

Synthesis of cross-linked triple helical DNAs possessing high affinity to triple helical DNA binding protein.

合成对三螺旋 DNA 结合蛋白具有高亲和力的交联三螺旋 DNA。

• 发表时间: 2005
• 期刊: Nucleic Acids Sympo.Ser. 49
• 作者: A.Shibata;Y.Ueno;M.Nakanishi;A.Matsuda;Y.Kitade
• 通讯作者: Y.Kitade

Alternate-strand triple-helix formation by 3'-3'-limked oligodeoxynucleotides composed of asymmetrical sequences

由不对称序列组成的3-3连接寡脱氧核苷酸形成交替链三螺旋

• 发表时间: 2004
• 期刊: Bioorg.Med.Chem.Lett. 14
• 作者: S.Hoshika;Y.Ueno et al.
• 通讯作者: Y.Ueno et al.

Synthesis of linked triple helical DNAs possessing high affinity to triple helical DNA binding protein.

合成对三螺旋 DNA 结合蛋白具有高亲和力的连接三螺旋 DNA。

• 发表时间: 2006
• 期刊: Bioorg.Med.Chem.Lett. 16
• 作者: A.Shibata;Y.Ueno;K.Shinbo;M.Nakanishi;A.Matsuda;Y.Kitade
• 通讯作者: Y.Kitade