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Nucleic Acids Research, 2001, Vol. 29, No. 9 1935-1942
© 2001 Oxford University Press

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

Melanie D. Keppler, Stephen Neidle1 and Keith R. Fox*

Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK and 1CRC Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK

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 µM, 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.

* To whom correspondence should be addressed. Tel: +44 2380 59 4374; Fax: +44 2380 59 4459; Email: k.r.fox{at}soton.ac.uk Present address:  Melanie Keppler, The Richard Dimbleby Department of Cancer Research, ICRF Laboratory, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK


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