DNA sequence preferences of several AT-selective minor groove binding ligands
DNA sequence preferences of several AT-selective minor groove binding ligands
We have examined the interaction of distamycin, netropsin, Hoechst 33258 and berenil, which are AT-selective minor groove-binding liganda, with synthetic DNA fragments containing different arrangements of AT base pairs by DNase I footprinting. For fragments which contain multiple blocks of (A/T)4 quantitative DNase I footprinting reveals that AATT and AAAA are much better binding sites than TTAA and TATA. Hoechst 33258 shows the greatest discrimination between these sites with a 50-fold difference in affinity between AATT and TATA. Alone amongst these ilgands, Hoechst 33258 binds to AATT better than AAAA. These differences in binding to the various AT-tracts are interpreted in terms of variations in DNA minor groove width and suggest that TpA steps within an AT-tract decrease the affinity of these ligands. The behaviour of each site also depends on the flanking sequences; adjacent pyrimidine-purine steps cause a decrease in affinity. The precise ranking order for the various binding sites is not the same for each ligand.
3385-3392
Abu-daya, Anita
97191275-138f-4405-b5e1-830540396ef0
Brown, Philip M.
c910b8df-2849-4b26-8f69-3ca330836e9b
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
11 September 1995
Abu-daya, Anita
97191275-138f-4405-b5e1-830540396ef0
Brown, Philip M.
c910b8df-2849-4b26-8f69-3ca330836e9b
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Abu-daya, Anita, Brown, Philip M. and Fox, Keith R.
(1995)
DNA sequence preferences of several AT-selective minor groove binding ligands.
Nucleic Acids Research, 23 (17), .
(doi:10.1093/nar/23.17.3385).
Abstract
We have examined the interaction of distamycin, netropsin, Hoechst 33258 and berenil, which are AT-selective minor groove-binding liganda, with synthetic DNA fragments containing different arrangements of AT base pairs by DNase I footprinting. For fragments which contain multiple blocks of (A/T)4 quantitative DNase I footprinting reveals that AATT and AAAA are much better binding sites than TTAA and TATA. Hoechst 33258 shows the greatest discrimination between these sites with a 50-fold difference in affinity between AATT and TATA. Alone amongst these ilgands, Hoechst 33258 binds to AATT better than AAAA. These differences in binding to the various AT-tracts are interpreted in terms of variations in DNA minor groove width and suggest that TpA steps within an AT-tract decrease the affinity of these ligands. The behaviour of each site also depends on the flanking sequences; adjacent pyrimidine-purine steps cause a decrease in affinity. The precise ranking order for the various binding sites is not the same for each ligand.
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Published date: 11 September 1995
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Funding Information:
This work was supported by grants from the Cancer Research Campaign, the Medical Research Council, the Royal Society and the Nuffield Foundation.
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Local EPrints ID: 475846
URI: http://eprints.soton.ac.uk/id/eprint/475846
ISSN: 0305-1048
PURE UUID: b9604faa-a09f-4a26-82ad-ceec047ff8ae
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Date deposited: 29 Mar 2023 16:45
Last modified: 18 Mar 2024 02:32
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Author:
Anita Abu-daya
Author:
Philip M. Brown
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