Footprinting Studies on Ligands which Stabilize DNA Triplexes: Effects on Stringency within a Parallel Triple Helix

Chandler, Simon P., Strekowski, Lucjan, Wilson, W. David and Fox, Keith R. (1995) Footprinting Studies on Ligands which Stabilize DNA Triplexes: Effects on Stringency within a Parallel Triple Helix. Biochemistry, 34 (21), 7234-7242. (doi:10.1021/bi00021a039).

Abstract

We have examined the effect of four triplex-binding ligands on the interaction of the oligodeoxynucleotides T₈NT₈ (N = A, G, C, T) with DNA fragments containing the sequences A₈XA₈.T₈- YT₈ (X = G, C, T; Y = C, G, A) by DNase I footprinting. The ligands form a series of quinoline derivatives with an alkylamine chain in the 4-position and different aryl substituents in the 2-position. By themselves these compounds do not alter DNase I digestion of the DNA duplexes at concentrations up to 100 µM. At a concentration of 10 µM they potentiate triplex formation, lowering the concentration of oligonucleotide required to produce a clear footprint by as much as 100-fold. As well as stabilizing triplexes which consist of well-characterized DNA triplets, they also promote the formation of complexes which contain central triplet mismatches. This reduction in the stringency of triple helix formation may be used to broaden the range of triplex target sequences and enable recognition at sites which contain short regions for which there are no good triplet matches.

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Contributors

Author: Keith R. Fox

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