DNA sequence specificity of triplex-binding ligands

Keppler, M.D., James, P.L., Neidle, S., Brown, T. and Fox, K.R. (2003) DNA sequence specificity of triplex-binding ligands. European Journal of Biochemistry, 270 (24). pp. 4982-4992. 10.1046/j.1432-1033.2003.03901.x.

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DOI: 10.1046/j.1432-1033.2003.03901.x

Abstract

We have examined the ability of naphthylquinoline, a 2,7-disubstituted anthraquinone and BePI, a benzo[e]pyridoindole derivative, to stabilize parallel DNA triplexes of different base composition. Fluorescence melting studies, with both inter- and intramolecular triplexes, show that all three ligands stabilize triplexes that contain blocks of TAT triplets. Naphthylquinoline has no effect on triplexes formed with third strands composed of (TC)n or (CCT)n, but stabilizes triplexes that contain (TTC)n. In contrast, BePI slightly destabilizes the triplexes that are formed at (TC)n (CCT)n and (TTC)n. 2,7-Anthraquinone stabilizes (TC)n (CCT)n and (TTC) n, although it has the greatest effect on the latter. DNase I footprinting studies confirm that triplexes formed with (CCT)n are stabilized by the 2,7-disubstituted amidoanthraquinone but not by naphthylquinoline. Both ligands stabilize the triplex formed with (CCTT) n and neither affects the complex with (CT)n. We suggest that BePI and naphthylquinoline can only bind between adjacent TAT triplets, while the anthraquinone has a broader sequence of selectivity. These differences may be attributed to the presence (naphthylquinoline and BePI) or absence (anthraquinone) of a positive charge on the aromatic portion of the ligand, which prevents intercalation adjacent to C+GC triplets. The most stable structures are formed when the stacked rings (bases or ligand) alternate between charged and uncharged species. Triplexes containing alternating C+GC and TAT triplets are not stabilized by ligands as they would interrupt the alternating pattern of charged and uncharged residues.

Item Type:Article
Uncontrolled Keywords:Anthraquinone; Molecular beacon; Naphthylquinoline; Triple helix; Triplex-binding ligand
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2750
Journal or Publication Title:European Journal of Biochemistry
Deposited By:Library Staff
Deposited On:20 Jan 2012 16:55
Last Modified:20 Jan 2012 16:55

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