Investigation of DNA Binding Oligopeptide

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，我们使用了我们以前开发的亲光基团如芳基叠氮和二苯甲酰基重氮甲烷作为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。

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.