Triplex selective 2-(2-naphthyl)quinoline compounds: Origins of affinity and new design principles
Triplex selective 2-(2-naphthyl)quinoline compounds: Origins of affinity and new design principles
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DOI：
10.1021/ja034181r
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发表时间：
2003-06-18
影响因子：
15
通讯作者：
Strekowski, L
中科院分区：
文献类型：
--
作者：
Chaires, JB;Ren, JS;Strekowski, L
采用竞争透析法研究了一系列取代2-（2-萘基）喹啉类化合物对三链DNA的结构选择性。研究了14种化合物与13种不同核酸序列和结构的相互作用。对于所研究的大多数化合物，发现对三链体结构poly dA：[poly dT]（2）的显著选择性。使用新开发的指标的竞争透析结合数据的定量分析表明，这些化合物是迄今为止合成的最具选择性的三链体结合剂。使用这些研究中使用的所有14种化合物的三重结合数据推导出定量结构-亲和力关系（QSAR）。定量构效关系表明，三链体结合自由能的主要有利决定因素是溶剂可及表面积。三链体结合亲和力与化合物电子亲和力和氢键供体的数量呈负相关。QSAR为设计改进的三链体结合剂提供了指导。
A novel competition dialysis assay was used to investigate the structural selectivity of a series of substituted 2-(2-naphthyl)quinoline compounds designed to target triplex DNA. The interaction of 14 compounds with 13 different nucleic acid sequences and structures was studied. A striking selectivity for the triplex structure poly dA:[poly dT](2) was found for the majority of compounds studied. Quantitative analysis of the competition dialysis binding data using newly developed metrics revealed that these compounds are among the most selective triplex-binding agents synthesized to date. A quantitative structure-affinity relationship (QSAR) was derived using triplex binding data for all 14 compounds used in these studies. The QSAR revealed that the primary favorable determinant of triplex binding free energy is the solvent accessible surface area. Triplex binding affinity is negatively correlated with compound electron affinity and the number of hydrogen bond donors. The QSAR provides guidelines for the design of improved triplex-binding agents.