Samudrala Ramakrishna, Zhang Xu, Wadkins Randy M, Mattern Daniell Lewis
Department of Chemistry and Biochemistry, Box 1848, University of Mississippi University, MS 38677, USA.
Bioorg Med Chem. 2007 Jan 1;15(1):186-93. doi: 10.1016/j.bmc.2006.09.075. Epub 2006 Oct 10.
A number of N,N'-disubstituted perylenetetracarboxylic diimides have been reported to bind effectively to DNA that adopts G-quadruplex motifs. In some cases, this binding may actively drive the transition from single-strand DNA to the quadruplex form. The perylenediimides in the reported cases all have amine-containing side chains, which are thought to interact with the grooves of the quadruplex and help dictate the selectivity of these compounds for quadruplex versus duplex DNA. We synthesized a polyethyleneglycol-swallowtailed (PEG-tailed) perylenediimide that is water-soluble even though it is uncharged. Binding to duplex and quadruplex DNA of this perylenediimide was studied by fluorescence quenching titrations under a variety of salt conditions, and the compound's effect on quadruplex formation was studied by non-denaturing gel electrophoresis. Our results indicate that while the molecule binds to single-stranded DNA quite effectively and with selectivity, it does not drive the transition of the DNA to the tetrameric quadruplex structure, supporting the idea that charge neutralization is a key component of perylene compounds that stabilize tetrameric quadruplexes.
据报道，一些N，N'-二取代苝四羧酸二亚胺能有效地与采用G-四链体基序的DNA结合。在某些情况下，这种结合可能会积极推动单链DNA向四链体形式的转变。在已报道的案例中，苝二亚胺都含有含胺侧链，据认为这些侧链与四链体的凹槽相互作用，并有助于决定这些化合物对四链体与双链DNA的选择性。我们合成了一种聚乙二醇燕尾式（PEG尾）苝二亚胺，尽管它不带电荷，但却是水溶性的。通过在各种盐条件下的荧光猝灭滴定研究了这种苝二亚胺与双链和四链体DNA的结合，并通过非变性凝胶电泳研究了该化合物对四链体形成的影响。我们的结果表明，虽然该分子能非常有效地且有选择性地与单链DNA结合，但它不会推动DNA向四聚体四链体结构的转变，这支持了电荷中和是稳定四聚体四链体的苝化合物的关键组成部分这一观点。
