DNA sequence specificity of a naphthylquinoline triple helix-binding ligand

Cassidy, Sarah A., Strekowski, Lucjan and Fox, Keith R. (1996) DNA sequence specificity of a naphthylquinoline triple helix-binding ligand. Nucleic Acids Research, 24 (21), 4133-4138. (doi:10.1093/nar/24.21.4133).

Abstract

We have examined the effect of a naphthylquinoline triplex-binding ligand on the formation of intermolecular triplexes on DNA fragments containing the target sites A₆G₆·C₆T₆ and G₆A₆·T₆C₆. The ligand enhances the binding of T₆C₂, but not T₂C₆, to A₆G₆·C₆T₆ suggesting that it has a greater effect on T·AT than C⁺·GC triplets. The complex with T₆C₂ is only stable below pH 6.0, confirming the requirement for protonation of the third strand cytosines. Antiparallel triplexes with GT-containing oligonucleotides are also stabilised by the ligand. The complex between G₅T₅ and A₆G₆·C₆T₆ is stabilised by lower ligand concentrations than that between T₅G₅ and G₆A₆·C₆T₆. The ligand does not promote the interaction with GT-containing oligonucleotides which have been designed to bind in a parallel orientation. Although the formation of antiparallel triplexes is pH independent, we find that the ligand has a greater stabilising effect at lower pH, suggesting that the active species is protonated. The ligand does not promote the binding of antiparallel GA-containing oligonucleotides at pH 7.5 but induces the interaction between A₅G₅ and G₆A₆·T₆C₆ at pH 5.5. Ethidium bromide does not promote the formation of any of these triplexes and destabilises the interaction of acridine-linked pyrimidine-containing third strands with these target sites.

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Contributors

Author: Keith R. Fox

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