Photochemical probe of DNA local structures

DNA局部结构的光化学探针

• 批准号: 15201046
• 负责人: SUGIYAMA Hiroshi
• 金额: $ 17.8万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15201046/
• 关键词: DNA; Z form DNA; photoreaction; H abstraction; DNA conformation; DNA probe; B-Z transition; 5-halouracil; 修飾塩基

DNA is polymorphic and exists in a variety of distinct conformations. Duplex DNA can adopt a variety of sequence-dependent secondary structures, which range from the canonical right-handed B form through to the left-handed Z form. However, the biological roles associated with the different structural conformations of DNA are not well understood because of the short lifetime of appearance of each structure and the difficulty in creating a system to demonstrate the DNA local structure. We found that incorporation of 8-methyl-2'-deoxyguanosine (m8G) and 8-methylguanosine (m8rG) into DNA dramatically stabilized the Z form, and facilitated the B-Z transition, even for AT-containing sequences. Developing a Z-stabilizing monomeric unit, the Z stabilizer, allowed us to understand the solution structure of Z-DNA and to reveal the specific 2'β-hydrogen abstraction that gives rise to the Z-form-specific 2'α-hydroxylation of the 5-halouracil-containing Z-form under UV irradiation. We also investigated the photoreaction of 5-halouracil in the A-form, B-form, G-quartet, and protein-induced DNA kinks. Hydrogen abstraction by 2'-deoxyuridin-5-yl generated from 5-halouracil under irradiation was atom specific and highly dependent on the DNA structure.

DNA是多态性的，并且以各种不同的构象存在。双链体DNA可以采用多种序列依赖的二级结构，其范围从典型的右手B形式到左手Z形式。然而，与DNA的不同结构构象相关的生物学作用还没有得到很好的理解，因为每个结构的出现寿命很短，并且很难建立一个系统来证明DNA的局部结构。我们发现，8-甲基-2 '-脱氧鸟苷（m8 G）和8-甲基鸟苷（m8 rG）掺入DNA显着稳定的Z形式，并促进B-Z转换，甚至对AT的序列。开发Z-稳定单体单元，Z稳定剂，使我们能够理解Z-DNA的溶液结构，并揭示特定的2 'β-氢提取，其在UV照射下引起含5-卤尿嘧啶的Z-形式的Z-形式特异性2' α-羟基化。我们还研究了5-卤脲嘧啶的光反应在A-型，B-型，G-四重态，和蛋白质诱导的DNA扭结。5-卤代尿嘧啶在辐照下生成的2 '-脱氧尿苷-5-基的夺氢作用具有原子特异性，并且高度依赖于DNA的结构。

项目成果

Biomolecule-based switching devices that respond inversely to thermal stimuli.

• DOI: 10.1021/ja044138j
• 发表时间: 2005-01
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Ryu Tashiro;H. Sugiyama

Efficient Genenation of 2'-Deoxyuridin-5-yl at 5'-(G/C)AA^xU^xU-3'(X=Br,I) Sequences in Duplex DNA under UV irradiation

紫外线照射下双链 DNA 中 5-(G/C)AA^xU^xU-3(X=Br,I) 序列的 2-脱氧尿苷-5-基的高效生成

• 发表时间: 2005
• 期刊: J.Am.Chem.Soc. 127・1
• 作者: Watanabe;T.;Sugiyama;H.
• 通讯作者: H.

Enantioselective DNA Alkylation by a Pyrrole-Imidazole S-CBI Conjugate

通过吡咯-咪唑 S-CBI 缀合物进行对映选择性 DNA 烷基化

• 发表时间: 2004
• 期刊: J.Am.Chem.Soc. 126・29
• 作者: Narita;A.;Sugiyama H.
• 通讯作者: Sugiyama H.

Tashiro, R., Sugiyama, H.: "Unique Charge Transfer Properties of the Four-base π-Stacks in Z-DNA"J.Am.Chem.Soc.. 125・50. 15282-15283 (2003)

Tashiro, R.、Sugiyama, H.：“Z-DNA 中四碱基 π 堆栈的独特电荷转移特性”J.Am.Chem.Soc. 125・50 (2003)。

Highly Efficient Photochemical 2'-Deoxyribonolactone Formation at the Diagonal Loop of a 5-Iodouracil-Containing Antiparallel G-Quartet

含 5-碘尿嘧啶的反平行 G-四重体的对角环上高效光化学 2-脱氧核糖内酯形成

• 发表时间: 2004
• 期刊: J.Am.Chem.Soc. 126・20
• 作者: Xu;Y.;Sugiyama;H.
• 通讯作者: H.