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DNA sequence specificity of triplex-binding ligands

DNA sequence specificity of triplex-binding ligands
DNA sequence specificity of triplex-binding ligands
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.
anthraquinone, molecular beacon, naphthylquinoline, riple helix, triplex-binding liganddouble-helical dna, c+center-dot-gc, human telomerase, stability, oligonucleotides, stabilization, recognition, parallel, coralyne, ph
0014-2956
4982-4992
Keppler, Melanie D.
6452c8eb-268a-47f4-955d-e1819df05333
James, Peter L.
ff85d76b-958d-428c-b864-f075c9770613
Neidle, Stephen
edf2d7ee-a257-4d4c-a3ea-b3c9c42b5ff3
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Keppler, Melanie D.
6452c8eb-268a-47f4-955d-e1819df05333
James, Peter L.
ff85d76b-958d-428c-b864-f075c9770613
Neidle, Stephen
edf2d7ee-a257-4d4c-a3ea-b3c9c42b5ff3
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f

Keppler, Melanie D., James, Peter L., Neidle, Stephen, Brown, Tom and Fox, Keith R. (2003) DNA sequence specificity of triplex-binding ligands. European Journal of Biochemistry, 270 (24), 4982-4992. (doi:10.1046/j.1432-1033.2003.03901.x).

Record type: Article

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.

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More information

Published date: 1 December 2003
Keywords: anthraquinone, molecular beacon, naphthylquinoline, riple helix, triplex-binding liganddouble-helical dna, c+center-dot-gc, human telomerase, stability, oligonucleotides, stabilization, recognition, parallel, coralyne, ph

Identifiers

Local EPrints ID: 19994
URI: http://eprints.soton.ac.uk/id/eprint/19994
ISSN: 0014-2956
PURE UUID: 0ebb4745-ddbd-4a0f-8202-6b2bb0144d1c
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

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Date deposited: 24 Feb 2006
Last modified: 16 Mar 2024 02:36

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Contributors

Author: Melanie D. Keppler
Author: Peter L. James
Author: Stephen Neidle
Author: Tom Brown
Author: Keith R. Fox ORCID iD

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