Abstract：
Spectroscopic, biochemical, and computational modelling studies have been used to assess the binding capability of a set of minor groove binding (MGB) ligands against the self-complementary DNA sequences 5\'-d(CGCACTAGTGCG)-3\' and 5\'-d(CGCAGTACTGCG)-3\'. The ligands were carefully designed to target the DNA response element, 5\'-WGWWCW-3\', the binding site for several nuclear receptors. Basic 1D 1H NMR spectra of the DNA samples prepared with three MGB ligands show subtle variations suggestive of how each ligand associates with the double helical structure of both DNA sequences. The variations among the investigated ligands were reflected in the line shape and intensity of 1D 1H and 31P-{1H} NMR spectra. Rapid visual inspection of these 1D NMR spectra proves to be beneficial in providing valuable insights on MGB binding molecules. The NMR results were consistent with the findings from both UV DNA denaturation and molecular modelling studies. Both the NMR spectroscopic and computational analyses indicate that the investigated ligands bind to the minor grooves as antiparallel side-by-side dimers in a head-to-tail fashion. Moreover, comparisons with results from biochemical studies offered valuable insights into the mechanism of action, and antitumor activity of MGBs in relation to their structures, essential pre-requisites for future optimization of MGBs as therapeutic agents.
摘要：
光谱学,生物化学，和计算建模研究已用于评估一组小沟结合（MGB）配体对自身互补DNA序列5'-d（CGCACTAGTGCG）-3'和5'-d（CGCAGTACTGCG）-3'的结合能力。配体经过精心设计，以靶向DNA反应元件，5\'-WGWWCW-3\',几个核受体的结合位点。用三种MGB配体制备的DNA样品的基本1D1HNMR光谱显示出细微的变化，表明每种配体如何与两种DNA序列的双螺旋结构缔合。所研究的配体之间的变化反映在1D1H和31P-{1H}NMR光谱的线形和强度中。这些1DNMR光谱的快速视觉检查被证明有利于提供关于MGB结合分子的有价值的见解。NMR结果与UVDNA变性和分子建模研究的结果一致。NMR光谱和计算分析均表明，所研究的配体以头对尾的方式作为反平行的并排二聚体与小沟结合。此外，与生化研究结果的比较提供了对作用机制的宝贵见解，以及与其结构相关的MGBs的抗肿瘤活性，未来优化MGBs作为治疗剂的必要先决条件。
