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A polarized-light spectroscopy study of interactions of a hairpin polyamide with DNA

A polarized-light spectroscopy study of interactions of a hairpin polyamide with DNA
A polarized-light spectroscopy study of interactions of a hairpin polyamide with DNA
We here study the interactions of a polyamide with large DNA, and compare to those of minor groove binder distamycin (DST), including high ligand/DNA binding ratios. Specific as well as nonspecific binding is probed using polarized-light spectroscopy combined with singular value decomposition analysis. Circular and linear dichroism data confirm binding geometries consistent with minor groove binding for both of the ligands. Interestingly, at high and intermediate ligand/DNA ratios the polyamide exhibits no significant sequence discrimination between mixed-sequence (calf thymus) and AT DNA as compared to DST. Each ligand is concluded to exhibit two different binding modes depending upon ligand/DNA ratio and nucleo-base sequence. At high binding ratios, distinct differences between the ligands are observed: circular dichroism spectra exciton effects provide evidence of bimolecular interactions of the polyamide when bound to AT-DNA, whereas no effects are seen with DST or mixed-sequence DNA. Also linear dichroism indicates that a change in binding geometry occurs at high polyamide/AT ratios, and that the effect occurs only with polyamide in contrast to DST. Since the effect is insignificant with DST, or with calf thymus DNA, it is concluded that it relates to the sizes of the ligands and the minor grooves, becoming critical in the limit of crowding.
0006-3495
904-911
Caesar, Christina.E.B.
978eba57-a489-4ddf-b6aa-2e704a345fe8
Johnsson, Richard.
698313fa-5e02-4b8f-a44e-b02c46f28ce0
Ellervik, Ulf
66e9a334-2450-44d6-9865-e281808da745
Fox, Keith.R.
9da5debc-4e45-473e-ab8c-550d1104659f
Lincoln, Per
f1edcf40-411d-4f54-bd94-d13394c011d4
Norden, Bengt
eeb831da-9170-4eb1-9682-1263cc27eb12
Caesar, Christina.E.B.
978eba57-a489-4ddf-b6aa-2e704a345fe8
Johnsson, Richard.
698313fa-5e02-4b8f-a44e-b02c46f28ce0
Ellervik, Ulf
66e9a334-2450-44d6-9865-e281808da745
Fox, Keith.R.
9da5debc-4e45-473e-ab8c-550d1104659f
Lincoln, Per
f1edcf40-411d-4f54-bd94-d13394c011d4
Norden, Bengt
eeb831da-9170-4eb1-9682-1263cc27eb12

Caesar, Christina.E.B., Johnsson, Richard., Ellervik, Ulf, Fox, Keith.R., Lincoln, Per and Norden, Bengt (2006) A polarized-light spectroscopy study of interactions of a hairpin polyamide with DNA. Biophysical Journal, 91, 904-911. (doi:10.1529/biophysj.105.080564).

Record type: Article

Abstract

We here study the interactions of a polyamide with large DNA, and compare to those of minor groove binder distamycin (DST), including high ligand/DNA binding ratios. Specific as well as nonspecific binding is probed using polarized-light spectroscopy combined with singular value decomposition analysis. Circular and linear dichroism data confirm binding geometries consistent with minor groove binding for both of the ligands. Interestingly, at high and intermediate ligand/DNA ratios the polyamide exhibits no significant sequence discrimination between mixed-sequence (calf thymus) and AT DNA as compared to DST. Each ligand is concluded to exhibit two different binding modes depending upon ligand/DNA ratio and nucleo-base sequence. At high binding ratios, distinct differences between the ligands are observed: circular dichroism spectra exciton effects provide evidence of bimolecular interactions of the polyamide when bound to AT-DNA, whereas no effects are seen with DST or mixed-sequence DNA. Also linear dichroism indicates that a change in binding geometry occurs at high polyamide/AT ratios, and that the effect occurs only with polyamide in contrast to DST. Since the effect is insignificant with DST, or with calf thymus DNA, it is concluded that it relates to the sizes of the ligands and the minor grooves, becoming critical in the limit of crowding.

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Published date: 5 May 2006

Identifiers

Local EPrints ID: 56631
URI: https://eprints.soton.ac.uk/id/eprint/56631
ISSN: 0006-3495
PURE UUID: 206dac83-b102-4013-a936-071283cec2c9
ORCID for Keith.R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

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Date deposited: 07 Aug 2008
Last modified: 14 Mar 2019 01:56

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