Stabilisation of TG- and AG-containing antiparallel DNA triplexes by triplex-binding ligands.
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.
Keppler
M D
MD
Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Neidle
S
S
Fox
K R
KR
D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001600:Berberine Alkaloids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000737:chemistry; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism
D000880:Anthraquinones; D001600:Berberine Alkaloids; D007211:Indoles; D008024:Ligands; D009841:Oligonucleotides; D011725:Pyridines; D011804:Quinolines; C102232:naphthylquinoline triple-helix-binding ligand; C051802:triplex DNA; C082732:3-methoxy-7H-8-methyl-11-((3'-amino)propylamino)benzo(e)pyrido(4,3-b)indole; C000666:coralyne; D004247:DNA; D003850:Deoxyribonuclease I