Stabilisation of TG-and AG-containing antiparrallel DNA triplexes by triplex-binding ligands

Abstract

Stabilisation of TG-and AG-containing antiparrallel DNA triplexes by triplex-binding ligands. We have used DNase I footprinting to examine the interaction of several tripler-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 CIM, 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 tripler, 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 tripler, 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 tripler motifs.