Investigation of DNA Binding Oligopeptide

DNA结合寡肽的研究

• 批准号: 09680568
• 负责人: NAKATANI Kazuhiko
• 金额: $ 2.05万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680568/
• 关键词: Photocrosslinking; oligopeptide; DNA

We have examined synthesis and evaluation of novel oligopeptide that bound sequence selectively to duplex DNA.While Dervan and co-workers have been intensively studied pyrrole polyamide compounds as a sequence selective DNA binding peptide, there are no obvious general principle for molecular design for such peptides. In order to gain insight into the general principle for designing sequence selective DNA-binding peptide, we have studied the combinatorial approach, that exploiting fraction of photocross linking as a measure for the efficiency of DNA binding. As a result, we have used photoaffiniti group such as aryl azide and dibenzoyldiazomethane that we have previously developped for G-acylating agent, but we could not get the efficient cross linking between DNA and peptide. Due to a lack of the positive control for binding as well as cross linking, we could not assess our approach properly. But these results clearly pointed out that photocross linking is not suitable for this purpose, because cross linking efficiency is not high as we expected. In the future, we are going to examine other types of cross linking reaction such as metal-catalyzed reaction.

我们已经研究了新型寡肽的合成和评价，这些寡肽可以选择性地与双链体DNA结合，而Dervan等人已经对吡咯聚酰胺化合物作为序列选择性DNA结合肽进行了深入的研究，但对于这类肽的分子设计还没有明显的一般原则。为了深入了解设计序列选择性DNA结合肽的一般原理，我们研究了利用光交联分数作为DNA结合效率的度量的组合方法。因此，我们已经使用了光亲合基团，如芳基叠氮和二苯甲酰重氮甲烷，我们已经开发的G-酰化剂，但我们不能得到DNA和肽之间的有效交联。由于缺乏结合和交联的阳性对照，我们无法正确评估我们的方法。但这些结果清楚地指出，光交联并不适合于这一目的，因为交联效率并不像我们预期的那样高。在未来，我们将研究其他类型的交联反应，如金属催化反应。

项目成果

"P-Cyano Substituted Benzophenone as an Excellent Photophore" Tetrahedron Lett. 39. 2779-2782 (1998)

“对氰基取代二苯甲酮作为优秀的发光体”四面体莱特。

中谷, 和彦: "p-Cyano Substituted 5-Benzoyldeoxy uridine" Tetrahedron Letters. 39. 5995-5998 (1998)

Nakatani, Kazuhiko：“对氰基取代的 5-苯甲酰脱氧尿苷”四面体快报 39。5995-5998 (1998)

中谷 和彦: "p-Cyano Substituted Beuzophenone as an Excelleut Photophore for One-Electron Oxidation of DNA." Tetrahedron Lett.印刷中.

Kazuhiko Nakatani：“对氰基取代 Beuzophenone 作为 DNA 单电子氧化的 Excelleut 发光体”，正在出版。

中谷, 和彦: "Highly Selective DNA alkylation at 5'side G of 5' GG3'" Journal of the American Chemical Society. 120. 11219-11225 (1998)

Nakatani, Kazuhiko：“5 GG3 5 侧 G 的高度选择性 DNA 烷基化”美国化学会杂志 120. 11219-11225 (1998)。

"Highly Selective DNA alkylation at 5'side G of 5'GG3'" JACS. 120. 11219-11225 (1998)

“5GG3 5 G 侧的高度选择性 DNA 烷基化”JACS。