Keppler M D, Neidle S, Fox K R
Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Nucleic Acids Res. 2001 May 1;29(9):1935-42. doi: 10.1093/nar/29.9.1935.
We have used DNase I footprinting to examine the interaction of several triplex-binding ligands with antiparallel TG- and AG-containing triplexes. We find that although a 17mer TG-containing oligonucleotide on its own fails to produce a footprint at concentrations as high as 30 microM, this interaction can be stabilised by several ligands. Within a series of disubstituted amidoanthraquinones we find that the 2,7- regioisomer affords the best stabilisation of this TG triplex, though the 1,8- isomer also stabilises this interaction to some extent. By contrast the 1,5- and 2,6- regioisomers show no interaction with TG triplexes. Similar studies with a 13mer AG-containing oligonucleotide show the opposite pattern of stabilisation: the 2,6- and 1,5- isomers stabilise this triplex, but the 2,7- and 1,8-compounds do not. The polycyclic compound BePI strongly stabilises TG- but not AG-containing triplexes, while a substituted naphthylquinoline interacts with both antiparallel triplex motifs.
我们运用DNA酶I足迹法来研究几种三链体结合配体与含反平行TG和AG的三链体之间的相互作用。我们发现,尽管一条含17个碱基的含TG寡核苷酸自身在高达30微摩尔的浓度下都无法产生足迹,但这种相互作用可被几种配体稳定。在一系列二取代氨基蒽醌中,我们发现2,7 - 区域异构体对这种TG三链体的稳定作用最佳,不过1,8 - 异构体在一定程度上也能稳定这种相互作用。相比之下,1,5 - 和2,6 - 区域异构体与TG三链体没有相互作用。对一条含13个碱基的含AG寡核苷酸进行的类似研究显示出相反的稳定模式:2,6 - 和1,5 - 异构体可稳定这种三链体,但2,7 - 和1,8 - 化合物则不能。多环化合物BePI能强烈稳定含TG但不含AG的三链体,而一种取代萘基喹啉与两种反平行三链体基序都有相互作用。