Investigation of DNA Binding Oligopeptide

我们研究了选择性结合序列与双链DNA结合的新型寡肽的合成和鉴定。虽然Dervan和他的同事们已经深入研究了吡咯聚酰胺化合物作为序列选择性DNA结合肽，但对于这类肽的分子设计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，我们研究了组合方法，即利用光交联率作为衡量DNA结合效率的指标。因此，我们使用了以前开发的芳基叠氮和二苯甲酰基重氮甲烷等光致亲和基团作为G-酰化剂，但我们无法得到DNA与多肽之间的有效交联剂。由于缺乏对结合和交联的积极控制，我们无法正确评估我们的方法。但这些结果清楚地指出，光交联并不适合于此目的，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.