Design and Synthesis of DNA-Cleaving Molecules

DNA 切割分子的设计与合成

• 批准号: 02453023
• 负责人: SAITO Isao
• 金额: $ 3.33万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02453023/
• 关键词: DNA Cleavage; Ene-diyne Antitumor Antibiotics; Artificial Restriction Enzym; Photo-DNA-Cleavage; Hydroxyl Radical Cenerator; 水酸ラジカル発生試薬; 光DNA切断

There has been great interest in designing reagents that bind to DNA duplex selectively at desired sequences. Such molecules equipped with a chemical or photochemical tag capable of modifying or cleaving DNA at the site of binding should have great prospects as "synthetic artificial restriction enzymes" and not least as gene-selective drugs. We have focused on the use of natural DNA-binders such as antitumor antibiotics, DNA-binding proteins or sequence-defined oligonucleotides in combination with photoactivated DNA-cleaving molecules. We have succeeded in designing a new sequence specific "photochemical DNA cleaver" that binds specifically to-5'-GG-3'sequence. This molecule named as "photo-Fenton-reagent" is widely used as a convenient source of hydroxyl radical. We also succeeded in designing a different type of DNA-cleaving molecules based on the conceit obtained from the work on the action mechanism of ene-diyne type antitumor antibiotics such as neocarzinostatin or esperamicin.

人们对设计在所需序列处选择性结合DNA双链体的试剂产生了极大的兴趣。这种分子装备有化学或光化学标记，能够在结合位点修饰或切割DNA，作为“合成的人工限制酶”，尤其是作为基因选择性药物，应该有很大的前景。我们一直专注于使用天然的DNA结合剂，如抗肿瘤抗生素，DNA结合蛋白或序列定义的寡核苷酸与光活化的DNA切割分子的组合。我们已经成功地设计了一种新的序列特异性的“光化学DNA切割器”，它特异性地结合到-5 '-GG-3'序列上。这种分子被称为“光芬顿试剂”，被广泛用作羟基自由基的方便来源。我们还成功地设计了一种不同类型的DNA切割分子的基础上，从工作中获得的构思的烯-二炔型抗肿瘤抗生素，如新carzinostatin或esperamicin的作用机制。

项目成果

杉本 弘: "Specific Detection of Cー4' Hydroxylated Abasic Sites Generated by Bleomycin and Neocarzinostatin in DNA" J.Am.Chem.Soc.112. 5250-5257 (1990)

Hiroshi Sugimoto：“DNA 中博来霉素和新制癌菌素生成的 C-4 羟基化无碱基位点的特异性检测”J.Am.Chem.Soc.112 (1990)。

杉山 弘: "Specific Detection of Cー4'Hydroxylated Abasic Sites Generated by Bleomycin and Neocarzinostatin in DNA" J.Am.Chem.Soc.112. 5252-5257 (1990)

Hiroshi Sugiyama：“DNA 中博来霉素和新制癌菌素生成的 C-4 羟基化无碱基位点的特异性检测”J.Am.Chem.Soc.112 (1990)。

永田 龍: "DNA Cleavage by Acyclic EneyneーAllene Systems related to Neocarzinostatin and EsperamicinーCalicheamicin" Tetrahedron Lett.31. 2907-2910 (1990)

Ryu Nagata：“与新制癌菌素和埃斯波霉素-卡利车霉素相关的无环烯-联烯系统的 DNA 切割”Tetrahedron Lett.31 (1990)。

杉山 弘: "Highly Sequence Selective Photreaction of 5ーBromouracilーContaining deoxyhexanucleotide" J.Am.Chem.Soc.112. 6720-6721 (1990)

Hiroshi Sugiyama：“含有 5-溴尿嘧啶的脱氧六核苷酸的高度序列选择性光反应”J.Am.Chem.Soc.112 6720-6721 (1990)。

S. Matsugo: "Bis (hydroperoxy) naphthaldiimide as a "Photo-Fenton Reagent", Sequence Specific Cleavage of DNA" Angew. Chem. Int. Ed. Engl.30. 1351-1353 (1991)

S. Matsugo：“双（氢过氧）萘二酰亚胺作为“光芬顿试剂”，DNA 的序列特异性切割”Angew。