A versatile mismatch recognition agent: Specific cleavage of a plasmid DNA at a single base mispair
A versatile mismatch recognition agent: Specific cleavage of a plasmid DNA at a single base mispair
复制标题
DOI：
10.1021/bi990255t
复制
发表时间：
1999-04-13
期刊：
影响因子：
2.9
通讯作者：
Barton, JK
中科院分区：
文献类型：
--
作者：
Jackson, BA;Alekseyev, VY;Barton, JK
[Rh(bpy)(2)(chrysi)](3+) 是一种新型、空间庞大的 DNA 嵌入剂，设计用于特异性结合 DNA 碱基错配附近的不稳定区域，并在光激活后切割 DNA 主链。这里该分子被证明是一种通用的和非常特异性的错配识别剂。在错配碱基周围所有可能的单碱基对序列环境中，超过 80% 的错配位点均观察到特异性 DNA 切割。此外，该综合体具有高度的场地特定性；它能够识别并光切割 2725 个碱基对线性化质粒异源双链体中的单碱基错配。空间要求较高的嵌入剂如 [Rh(bpy)(2)(chrysi)](3+) 可能在突变检测系统和错配特异性化疗剂中都有应用。
[Rh(bpy)(2)(chrysi)](3+) is a novel, sterically bulky DNA intercalator that has been designed to bind specifically in the destabilized regions near DNA base mismatches and, upon photoactivation, to cleave the DNA backbone. Here the molecule is shown to be both a general and remarkably specific mismatch recognition agent. Specific DNA cleavage is observed at over 80% of mismatch sites in all the possible single base pair sequence contexts around the mispaired bases. Moreover, the complex is highly site-specific; it is shown to recognize and photocleave at a single base mismatch in a 2725 base pair linearized plasmid heteroduplex. Sterically demanding intercalators such as [Rh(bpy)(2)(chrysi)](3+) may have application both in mutation detection systems and as mismatch-specific chemotherapeutic agents.