Investigation of DNA Binding Oligopeptide

我们研究了一种新的寡肽的合成和评价，这种寡肽选择性地结合序列到双链DNA。虽然Dervan和同事们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，但对于这种肽的分子设计并没有明显的通用原则。为了深入了解设计序列选择性DNA结合肽的一般原理，我们研究了组合方法，利用光交联的分数作为DNA结合效率的衡量标准。因此，我们使用了我们之前开发的芳基叠氮和二苯甲酰重氮甲烷等光亲和性基团作为g -酰化剂，但我们无法得到DNA与肽之间有效的交联。由于缺乏对结合和交联的阳性控制，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用于此目的，因为交联效率并不像我们预期的那么高。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.