特异性识别DNA的吡咯-咪唑多聚酰胺的研究进展

Progress on Pyrrole-Imidazole Polyamides Specifically Recognizing DNA

吡咯 咪唑多聚酰胺为一类人工合成的主要由五元杂环化合物N 甲基吡咯 (Py)、N 甲基咪唑(Im)和N 甲基 3 羟基吡咯 (Hp)芳香氨基酸组成的 ,经酰胺键连接的人工小分子配体。它们具有与天然DNA结合蛋白相媲美的DNA特异性识别和结合能力。近 2 0年来 ,对此类化合物的研究取得了重要进展 ,确定了简单的氨基酸对识别碱基对的规则 ,研究了多种方式连接的吡咯 咪唑多聚酰胺与DNA小沟结合模式 ,合成了多种双功能吡咯 咪唑多聚酰胺 ,且吡咯 咪唑多聚酰胺能穿过细胞膜 ,具有在体内外调节基因表达的作用。

Pyrrole-imidazole polyamides containing N-methylpyrrole, N-methylimidazole and N-methyl-3-hydroxypyrrole aromatic amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of naturally occuring DNA binding proteins. In past two decades, a lot of polyamides including some bifunctional ligands that can specifically alkylate and cleavage DNA have been synthesized and simple paring rules and various binding models for the minor groove of the double helix developed that allow the design of ligands for predetermined DNA sequences. Polyamides are also showed to permeate cells, potentially regulating transcription of specific genes.